{"title":"Plasma High-Mobility Group Box-1 and Galectin-9 in Patients with Trauma and Their Prognostic Potentials.","authors":"Toshiro Niki, Haorile Chagan-Yasutan, Daisuke Furushima, Toshio Hattori, Yugo Ashino, Satoshi Yamanouchi, Shigeki Kushimoto","doi":"10.1620/tjem.2024.J130","DOIUrl":"10.1620/tjem.2024.J130","url":null,"abstract":"<p><p>Damage-associated molecular patterns (DAMPs) are endogenous molecules released from damaged tissues and elicit strong inflammatory responses of the host. Hence, they are supposed to play essential roles in the disrupted immune homeostasis after traumatic injuries. We examined plasma levels of galectin-9 (Gal-9), an immune checkpoint molecule as well as a DAMP, and a representative DAMP, high-mobility group box-1 (HMGB-1) in the trauma patient. Gal-9 was very high at admission, declined swiftly, and reached the normal level in 48 hours, while HMGB-1 was highest at admission, declined in 24 hours, then stagnated through the assessment period of 7 days with a level much higher than that of healthy subjects. The concentration of these DAMPs at admission correlated well with each other. HMGB-1 correlated with 6 prognostic parameters compared to only 2 for Gal-9, which reflects HMGB-1 but not Gal-9 could discriminate between survived and deceased patients. Receiver-operating characteristic (ROC) curve analysis demonstrated that plasma HMGB-1 possesses a moderate prognostic potential to discriminate deceased patients from survivors. Collectively, HMGB-1 has a potential to make a valuable blood biomarker for trauma, possibly in combination with other blood biomarkers.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":"261-269"},"PeriodicalIF":1.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591489","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":"Study on Cellular Mechanism of Improving Inflammatory Effect of Gastrodin.","authors":"Xue Zheng, Taowu Gong, Wanqiu Yu, Shan Xu, Chunchun Tang, Yuanping Zhong, Zhaoqiong Zhu","doi":"10.1620/tjem.2024.J141","DOIUrl":"10.1620/tjem.2024.J141","url":null,"abstract":"<p><p>Neuroinflammation is a major pathological mechanism of neurodegenerative disease-triggered cognitive disorders. Currently, no preventative measures or therapies are available. Gastrodin (GAS), an effective monomer derived from Gastrodia, is considered to be an anti-inflammatory candidate to attenuate microglia-induced neuroinflammation and neurodegenerative diseases. The present study first modelled the inflammatory activation of BV2 cells, which was induced by lipopolysaccharide (LPS) at the molecular level. The optimal concentration of GAS was screened out to preliminarily investigate its role in improving the inflammatory activation of BV2 cells during cellular death. Then, the research further discussed how GAS ameliorated inflammation via regulating ferroptosis. According to the results of our study, GAS up-regulates downstream heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) expression while lowers reactive oxygen species (ROS) expression by Nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear transposition. Experimental results showed that 100 µM is the optimal concentration for gastrodin in the inflammatory activation model. GAS can promote Nrf2 nuclear translocation and the expression of HO-1 and NQO1 while reduce ROS level. Therefore, GAS can regulate ferroptosis in LPS-induced BV2 cellular inflammation model, thus attenuating inflammatory occurrence. In conclusions, GAS is considered to be an anti-inflammatory candidate that acts in LPS-induced BV2 cellular inflammation model by regulating ferroptosis.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":"249-259"},"PeriodicalIF":1.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740735","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":"Identification of Two Subtypes with Distinct Immune Features in Lung Adenocarcinoma by Utilizing Immune and Metabolism-Related Genes to Assist Immunotherapy.","authors":"Mengna Wang, Hongbo Xia","doi":"10.1620/tjem.2024.J086","DOIUrl":"10.1620/tjem.2024.J086","url":null,"abstract":"<p><p>This work was designed to explore the value of immune and metabolism-related genes (IMRGs) in lung adenocarcinoma (LUAD) prognosis, with the intention of aiding the application of immunotherapy in LUAD patients. Differential gene expression analysis was conducted using The Cancer Genome Atlas (TCGA)-LUAD data. After merging and deduplication, an intersection was taken with LUAD differential genes to acquire IMRGs. 716 IMRGs were utilized for LUAD clustering, resulting in the stratification of LUAD patients into two subtypes. Cluster-1 demonstrated higher immunophenoscore and lower tumor immune dysfunction and exclusion scores, indicating that cancer patients in cluster-1 were more likely to benefit from immune checkpoint inhibitor therapy. Somatic mutation analysis revealed higher mutation rates in both sample and gene levels for cluster-2 compared to cluster-1. Additionally, we predicted ten prospective candidate drugs, including Teniposide and phloretin, for LUAD patients. LUAD was stratified into two subtypes with distinct molecular features based on IMRGs. These subtypes exhibited pronounced differences in immune processes, checkpoints, genetic mutations, and drug sensitivity. Our endeavor has furnished invaluable insights into comprehending the molecular characteristics of LUAD, potentially enhancing the precision of immunotherapeutic strategies tailored for LUAD.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":"1-9"},"PeriodicalIF":1.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133842","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}
Miki Yamauchi, Jun Watanabe, Yoshikazu Kawazuma, Kazuhiko Kotani
{"title":"Factors Related to Recruitment and Retention of Doctors on Remote Islands: A Systematic Review.","authors":"Miki Yamauchi, Jun Watanabe, Yoshikazu Kawazuma, Kazuhiko Kotani","doi":"10.1620/tjem.2025.J048","DOIUrl":"https://doi.org/10.1620/tjem.2025.J048","url":null,"abstract":"","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035689","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}
Yanwei Wang, Huifan Liu, Yali Feng, Shujuan Wu, Jingxuan He, Lei Cao
{"title":"Sulforaphane Inhibits LPS-induced Macrophage PANoptosis via TLR4/NFκB Pathway: A Potential Therapeutic Strategy for Acute Lung Injury.","authors":"Yanwei Wang, Huifan Liu, Yali Feng, Shujuan Wu, Jingxuan He, Lei Cao","doi":"10.1620/tjem.2024.J105","DOIUrl":"10.1620/tjem.2024.J105","url":null,"abstract":"<p><p>Sepsis-induced acute lung injury (ALI) has a high mortality rate, and cytokine storm is its feature. PANoptosis is a new type of cell death including apoptosis, pyroptosis and necroptosis. The aim of this study is to detect the PANoptosis level of lung macrophages, and to elucidate the new mechanism of sulforaphane (SFN) in sepsis-induced ALI. In septic animal model, the fluorescent staining of Caspase-8, GSDMD and p-MLKL and ASC/Caspase-8/RIPK3 PANoptosome in lung macrophages was performed. Lipopolysaccharide (LPS) was used to induce macrophages to construct cell model of sepsis. The proportion of dead cells was detected by PI staining, and the expression of Bax, GSDMD-N, NLRP3 and p-MLKL was detected by western blotting. Search for the target genes of SFN and sepsis by network pharmacology. Molecular docking analysis confirmed the binding between SFN and TLR4. The protein levels of TLR4, P65 and p-P65 were detected by western blotting. The transcriptional levels of inflammatory factors were detected by qPCR. The expression of Caspase-8, GSDMD, p-MLKL and PANoptosome in septic lung macrophages was significantly increased, suggesting PANoptosis was up-regulated. LPS induced macrophages death and increased protein levels of Bax, GSDMD-N, NLRP3 and p-MLKL, which were reversed by pretreatment with SFN. Network pharmacology and molecular docking demonstrated that SFN could bind to TLR4 and inhibit NFκB pathway. The mRNA levels of pro-inflammatory factors IL6, CXCL16, iNOS and IL18 were down-regulated by SFN. SFN might alleviate LPS-induced macrophage PANoptosis through TLR4/NFκB pathway, thereby inhibiting macrophage inflammation and becoming a potential therapeutic drug for sepsis-induced ALI.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":"239-248"},"PeriodicalIF":1.7,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366555","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}
Yanqian Su, Huijuan Shi, Jue Tang, Siqi Zhao, Xuan Li, Jing Wang, Yanling He
{"title":"Association Between Triglyceride Glucose Index and All-Cause Mortality in the Psoriasis Patients.","authors":"Yanqian Su, Huijuan Shi, Jue Tang, Siqi Zhao, Xuan Li, Jing Wang, Yanling He","doi":"10.1620/tjem.2024.J089","DOIUrl":"10.1620/tjem.2024.J089","url":null,"abstract":"<p><p>Triglyceride glucose (TyG) index has been discovered to be significantly associated with a higher risk of mortality. However, the specific association between the TyG index and all-cause mortality in psoriasis patients remains unclear. Data of this study came from the National Health and Nutrition Examination Survey (NHANES). The weighted multivariable Cox regression models and restricted cubic spline (RCS) models were applied to assess the association between the TyG index as continuous variables and tertiles and the risk of mortality. Kaplan-Meier (KM) methods were used to plot survival curves to describe the survival of participants. Additionally, sensitivity and subgroup analyses were conducted to test the robustness of the results. Psoriasis participants who died had substantially higher TyG index than those survived (9.00 ± 0.68 vs. 8.64 ± 0.60, P = 0.008). Multivariable Cox regression showed that TyG index was positively associated to the risk of all-cause mortality (hazard ratios (HR) 1.78, 95% confidence intervals (CI): 1.13-2.81; P = 0.012) after fully adjustment. After converting TyG index from a continuous variable to a categorical variable by tertiles, the unadjusted, partly-adjusted and fully adjusted HR for risk of all-cause mortality were 3.96 (95% CI: 1.47-10.7; P = 0.007), 3.10 (95% CI: 1.20-7.99; P = 0.019) and 3.05 (95% CI: 1.14-8.16; P = 0.027) in participants in tertile 3 of TyG index, compared with tertile 1. The significance of the association persisted across sensitivity and subgroup analysis. The TyG index was positively correlated with the risk of all-cause mortality among psoriasis. These findings suggest that TyG index may be a promising predictor of all-cause mortality for the psoriasis patients during the long-term follow-up.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":"201-209"},"PeriodicalIF":1.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296186","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":"Effects of 15 Years of Continuous Treatment with Bisphosphonate on Japanese Postmenopausal Osteoporosis Patients: An Observational Study.","authors":"Kousuke Iba, Megumi Hanaka, Makoto Emori, Kenichi Takashima, Atsushi Teramoto, Junichi Takada","doi":"10.1620/tjem.2024.J124","DOIUrl":"10.1620/tjem.2024.J124","url":null,"abstract":"<p><p>Bisphosphonate (BP) is mainly used for the treatment of osteoporosis because of its efficacy in increasing bone mineral density (BMD) and reducing osteoporotic fractures. Previous large-scale studies indicated that continuous 10-year treatment with BP was effective for osteoporosis treatment. However, several studies indicated an increase in the risk of serious adverse events such as atypical femoral fracture on prolonged BP treatment. The benefits and risks associated with long-term BP therapy are controversial. On the other hand, the effects of BP for more than 10 years are unknown because of few previous studies. The aim of this study to investigate effects of continuous 15-year treatment with BP on Japanese postmenopausal osteoporosis patients. The study was a retrospective observational study. Fifteen of the 55 patients, who had already received a 10-year course of oral BP treatment in our previous study, continued the treatment for an additional 5 years. All patients made the choice additional BP treatment with informed consent. BMD; hip structural analysis (HSA); limbs-muscle volume; and serum total alkaline phosphatase, tartrate-resistant acid phosphatase-5b, calcium and phosphate levels were measured for 5 years in the 15 patients. BMD values at the lumbar spine were significantly increased at 15 years in comparison with that at 10 years. Section modulus of HSA for the intertrochanter was significantly increased at 15 years. No subsequent fractures or serious adverse events were observed. We demonstrated favorable effects of an additional 5 years of BP treatment in postmenopausal osteoporosis patients who had already received a continuous 10-year treatment.</p>","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":"229-237"},"PeriodicalIF":1.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591490","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 Significance of miR-4638-5p in Patients with Sepsis and Its Regulatory Role in the LPS-Induced Inflammatory Response.","authors":"Yuanming Bai, Jing Yang, Xin Liu, Jianyuan Huang","doi":"10.1620/tjem.2025.J045","DOIUrl":"https://doi.org/10.1620/tjem.2025.J045","url":null,"abstract":"","PeriodicalId":23187,"journal":{"name":"Tohoku Journal of Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988207","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}