The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Current issue
October
Displaying 1-12 of 12 articles from this issue
Regular Contribution
  • Fuwang Zhang, Wenfang Cui
    Article type: Regular Contribution
    2025Volume 267Issue 2 Pages 133-139
    Published: 2025
    Released on J-STAGE: October 09, 2025
    Advance online publication: May 22, 2025
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    The study investigated the relationship between ratio of D-dimer to brain natriuretic peptide (BNP), large right-to-left shunt (RLS) by contrast-enhanced transthoracic echocardiography (c-TTE), and cryptogenic stroke (CS) in patent foramen ovale (PFO). The study populations were composed of 61 patients with PFO who had been scheduled for transcatheter closure for CS (n = 20) or migraine (n = 41). Large RLS was defined as more than 20 microbubbles at rest and during the Valsalva maneuver by c-TTE. The PFO/CS group exhibited a higher proportion of large RLS at rest (3 vs. 0, P = 0.032) and during the Valsalva maneuver (14 vs. 11, P = 0.002) than the PFO/migraine group. More specifically about PFO characteristics, the height of PFO in the PFO/CS group was higher than that in the PFO/migraine group, and the proportion of atrial septal aneurysm in the PFO/CS group was higher than that in the PFO/migraine group (8 vs. 4, P = 0.013). The ratio of D-dimer to BNP was found to be significantly higher in the PFO/CS group than the PFO/migraine group (P = 0.010). The multiple logistic regression analysis showed that a large RLS during Valsalva maneuver and a high ratio of D-dimer to BNP were independent factors associated with CS in PFO. The study demonstrates that a high ratio of D-dimer to BNP and large RLS by c-TTE as risk factors for CS in PFO.

  • Wei-Ying Chen, Jin Li, Dan Xia
    Article type: Regular Contribution
    2025Volume 267Issue 2 Pages 141-150
    Published: 2025
    Released on J-STAGE: October 10, 2025
    Advance online publication: January 16, 2025
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    This randomized controlled trial compared the efficacy of cognitive-behavioral therapy for insomnia (CBT-I) vs. CBT-I without Jacobson progressive muscle relaxation (JPMR) in maintenance hemodialysis (MHD) patients. A total of 160 MHD patients with insomnia were randomly assigned to either the CBT-I group, which received a 7-week CBT-I program combined with JPMR, or the CBT-I without JPMR group, which underwent the same CBT-I program without the inclusion of JPMR. The 7-week intervention incorporated sleep restriction, stimulus control, cognitive restructuring, and relaxation techniques. Outcomes were assessed at weeks 0, 4, 8, and 12 using the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Modified Fatigue Impact Scale (MFIS), Hospital Anxiety and Depression Scale (HADS), and SF-36 Health Survey. The CBT-I group showed significantly greater and sustained improvements in insomnia severity, sleep quality, fatigue, anxiety, depression, and overall quality of life compared to the CBT-I without JPMR group. Improvements in ISI and PSQI scores, as well as reductions in fatigue, anxiety, and depression, were observed as early as week 4 and became more pronounced by week 12. Additionally, quality of life improved significantly across all SF-36 dimensions in the CBT-I group. This study demonstrated that the CBT-I is more effective than CBT-I without JPMR in addressing insomnia, fatigue, anxiety, depression, and quality of life in MHD patients, offering a comprehensive approach to improving sleep and mental well-being in this population.

  • Ying Guo, Yuyang Miao, Kailin Wang, Jin Tan, Zhen Jiao, Qiang Zhang
    Article type: Regular Contribution
    2025Volume 267Issue 2 Pages 151-162
    Published: 2025
    Released on J-STAGE: October 17, 2025
    Advance online publication: January 30, 2025
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    Intermittent hypoxia (IH) induced nerve cells apoptosis is an important cause of secondary cognitive dysfunction to obstructive sleep apnea (OSA) and may be a potential therapeutic target for this disease. This study was to explore the most appropriate conditions on the action of nano lipid bubbles (NLBs) which were applied to treat nerve injury caused by IH. An IH model of in vitro nerve cells was constructed. NLBs were created by reciprocating differential pressure method and magnetic xenon NLBs (Xe-NLBs) were created by magneto internal heat bubble generation (MIHBG). Morphology and stability of NLBs were tested via Transmission electron microscope (TEM) and dynamic light scatterer (DLS). Endocytosis and nerve injury after NLBs treatment were assessed by Immunofluorescence and MTT assay. Both Xe-NLBs (107 bubbles/ml, prepared by the reciprocal differential pressure method) and magnetic Xe-NLBs (107 bubbles/ml, prepared by the MIHBG) administration for up to 6 h after IH onset reduced IH induced nerve injury, and the magnetic Xe-NLBs showed a better neuroprotection, whereas O2, H2, and N2-NLBs did not show significant effects. An equal volume of saturated xenon aqueous solution (Xe-solution) exhibited similar results although these therapeutic effects were far less than those of magnetic Xe-NLBs. These results revealed that Xe was the most effective neuroprotective gas in IH-induced nerve injury. Xe-NLBs prepared by the MIHBG have achieved the maximal therapeutic effects by 107 bubbles/ml with 6 h treatment time under IH.

  • Lei Xi, Wentao Li, Baodi Deng, Feng Zhao
    Article type: Regular Contribution
    2025Volume 267Issue 2 Pages 163-175
    Published: 2025
    Released on J-STAGE: October 17, 2025
    Advance online publication: February 13, 2025
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    Retinoblastoma (RB), the most prevalent intraocular cancer in children, has complex pathogenesis resulting from various genetic interactions. Research revealed that orthodenticle homeo box 2 (OTX2) has certain connection with reticulon-4 (RTN4) in regulating the angiogenesis in RB, but the molecular mechanism has not been borne out yet. This study employed an array of in vitro techniques to explore the OTX2/RTN4 interaction and its effects on RB. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and dual-luciferase reporter assays were performed to assess gene and protein expression levels. Functional impacts were evaluated through cell culture, transfection, cell viability, clone formation, wound scratch, Transwell, and in vitro tube angiogenesis assays. These methods specifically unveiled the roles of siRNA-mediated RTN4 knockdown (siRTN4), short hairpin RNA-mediated OTX2 knockdown (shOTX2), and OTX2 overexpression in modulating cellular behaviors indicative of tumorigenesis and angiogenesis. Our results demonstrated that OTX2 positively regulated RTN4, thus promoting RB cell proliferation, migration, invasion, and angiogenesis, which was significantly attenuated by knockdown of OTX2 or RTN4, but enhanced by OTX2 overexpression. OTX2 overexpression also counteracted the inhibitory effects of RTN4 knockdown on angiogenesis and tumor dynamics. In conclusion, the OTX2/RTN4 axis plays a critical role in the progression of RB by promoting malignant cellular phenotypes and angiogenesis.

  • Yue Zhu, Hui Cheng, Min Xu, Guimei Li, Yanling Cui
    Article type: Regular Contribution
    2025Volume 267Issue 2 Pages 177-183
    Published: 2025
    Released on J-STAGE: October 22, 2025
    Advance online publication: February 13, 2025
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    This study elucidated the effect and underlying mechanism of Curcuma aeruginosa Roxb. [C. zedoaria non Rosc.] (CAR) in human papillomavirus (HPV)-related cervical cancer treatment through a network pharmacology approach. Serum containing CAR was prepared using SD rats. The activities of CAR in HPV-related cervical cancer cell viability and migration/invasion were detected by using cell count kit and Transwell assays. Compounds in CAR and their targets were collected from TCMSP and SymMap. The cervical cancer-associated targets were searched from GeneCards and TTD databases. Genes targeted by HPV in human were collected from VISDB database. The networks were constructed using all the targets/compounds or HPV cervical cancer-related targets/compounds. The binding affinity of Furanodiene with Dipeptidyl peptidase IV (DPP4) was determined by the molecular docking method in CB-Dock2. Overexpression of DPP4 was used to discover the effects of dipeptidyl peptidase IV protein on anticancer activity of CAR. CAR-containing serum inhibited the cell viability and migration/invasion of SiHa and Ca Ski cells. Three CAR targets, DPP4, Nitric-oxide synthase, endothelial (NOS3), and Apoptosis regulator Bcl-2 (BCL2) were common with cervical cancer-related genes and HPV-targeted genes. NOS3 was targeted by Furanodiene, BCL2 was targeted by beta-elemene, and DPP4 was targeted by (-)-Epoxycaryophyllene, Zingiberene, Furanodiene, etc. Molecular docking of DPP4 with Furanodiene showed two positions with a Vina score of –6.8. Overexpression of DPP4 reversed the anticancer effects of CAR on HPV-related cervical cancer cells. CAR had inhibitory effects on HPV cervical cancer, possibly by downregulating the expression of DPP4.

  • Xiangli Shen, Yushan Chen, Lili Yu, Junmeng Zheng, Shasha Shang, Jianr ...
    Article type: Regular Contribution
    2025Volume 267Issue 2 Pages 185-201
    Published: 2025
    Released on J-STAGE: October 24, 2025
    Advance online publication: March 06, 2025
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    To investigate the mechanisms by which berberine (BBR) improves macrophage efferocytosis dysfunction and alleviates inflammation induced by oxidized low-density lipoprotein (ox-LDL), a macrophage efferocytosis dysfunction model was established by inducing RAW264.7 cells with ox-LDL. This model was employed to assess the enhancing efferocytosis and anti-inflammatory effects of BBR in vitro. Flow cytometry was used to detect the efferocytosis function of RAW264.7 cells, while enzyme-linked immunosorbent assay (ELISA) measured inflammatory factor levels. Reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting were utilized to assess mRNA and protein expression levels of the PPARγ/LXRα axis and efferocytosis-related molecules. Results showed that efferocytosis significantly increased in RAW264.7 cells following protective intervention with BBR, evidenced by markedly higher expression of efferocytosis-related molecules GAS6, MerTK, and ABCA1 compared to the ox-LDL group. Additionally, BBR reduced the production of pro-inflammatory cytokines, enhanced the release of pro-resolving mediators, and mitigated inflammation. BBR enhanced efferocytosis by upregulating the expression of PPARγ/LXRα proteins and mRNA. In the presence of the PPARγ inhibitor (GW9662) and the LXRα inhibitor (GSK2033), levels of GAS6, MerTK, and ABCA1, as well as the expression levels of PPARγ/LXRα proteins and mRNA, were significantly lower compared to the BBR group. Furthermore, the inhibition of efferocytosis and production of anti-inflammatory cytokines were markedly weaker in the BBR+GW9662 and BBR+GSK2033 groups. These findings suggest that BBR exerts effects through the PPARγ/LXRα pathway, enhancing efferocytosis, regulating macrophage phenotype, inhibiting pro-inflammatory cytokine production, promoting pro-resolving mediators release, and demonstrating anti-atherosclerosis effects.

  • Chang-wei Peng, Pei-li Ma, Hai-tao Dai
    Article type: Regular Contribution
    2025Volume 267Issue 2 Pages 203-216
    Published: 2025
    Released on J-STAGE: October 22, 2025
    Advance online publication: March 27, 2025
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    Supplementary material

    The antisense transcripts play key roles in the pathogenesis of cancer. Long noncoding RNA (lncRNA) ACTA2 antisense RNA 1 (ACTA2-AS1) has been reported to inhibit the development of several cancers. In this article, the roles of ACTA2-AS1 and ACTA2 in prostate cancer (PCa) were investigated. The ACTA2-AS1 and ACTA2 expression levels in PCa samples were evaluated using GEPIA database. RT-qPCR or western blotting was used to measure their expression in PCa cells. The effects of ACTA2-AS1 and ACTA2 on PCa cell proliferation, cell cycle, migration, invasion, epithelial-mesenchymal transition (EMT), and apoptosis were detected using colony formation, wound healing, transwell, flow cytometry, and western blotting. Xenograft tumor models were used to evaluate the effects of ACTA2-AS1 and ACTA2 on tumor growth. Subcellular localization, luciferase report, and RNA stability assay were performed to detect how ACTA2-AS1 modulates ACTA2 expression in PCa. We found that ACTA2-AS1 and ACTA2 were downregulated in PCa and there was a positive relationship between ACTA2-AS1 expression and ACTA2 expression in PCa samples. Overexpression of ACTA2-AS1 inhibited cell proliferation, cell cycle, migration, invasion, EMT, and promoted apoptosis, while knockdown of ACTA2-AS1 exerted opposite results. Silencing ACTA2 reversed the antitumor effect of ACTA2-AS1 overexpression on PCa in vitro and in vivo. Mechanistically, ACTA2-AS1 positively modulated ACTA2 expression by enhancing ACTA2 promoter activity to stabilize ACTA2 mRNA. Overall, ACTA2-AS1 inhibits PCa cell growth, migration, invasion, EMT, tumor growth and promotes apoptosis by enhancing ACTA2 mRNA stability, suggesting that ACTA2-AS1 may be an effective therapeutic target for PCa.

  • Urara Akasaka, Miki Takahashi, Asuko Sekimoto, Hideyuki Hirayama, Maho ...
    Article type: Regular Contribution
    2025Volume 267Issue 2 Pages 217-224
    Published: 2025
    Released on J-STAGE: October 23, 2025
    Advance online publication: November 07, 2024
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    Supplementary material

    When patients express emotional concerns, empathic responses from medical staff reduce their psychological distress. The NURSE program was developed in Japan to facilitate the emotional expression of patients. The NURSE program consists of five communication skills: (1) naming, (2) understanding, (3) respecting, (4) supporting, and (5) exploring. However, this program has no evaluation tool. Therefore, we developed a five-item scale based on the “NURSE” communication skills program and confirmed its validity. We conducted a cross-sectional self-administered questionnaire survey using the test-retest method in December 2022. The potential participants were aged ≥ 20 who had been hospitalized for one week or more within the past year and registered with an Internet research company. For concurrent validity, we collected data using the Japanese version of the Feeling Heard and Understood Scale (FHU) and Clinician & Group Survey Consumer Assessment of Healthcare Providers and Systems (CG-CHAPS). A total of 608 patients participated in the study. There were 306 (50.3%) male participants, with a mean age of 57.0 ± 16.8 years. The mean ± SD of the total score was 12.2 ± 4.3, and Cronbach’s alpha coefficient was 0.95. The overall intraclass correlation coefficient was 0.54. Spearman’s correlation coefficients for this scale and the FHU and for this scale and CG-CHAPS were 0.66 and 0.68, respectively (p < 0.0001). This study developed a scale to evaluate the communication skills of nurses, based on the NURSE program, to facilitate emotional expression and demonstrated sufficient validity and moderate reliability.

  • Yong Jiang, Jing-Ping Yang, Qin Liu
    Article type: Regular Contribution
    2025Volume 267Issue 2 Pages 225-233
    Published: 2025
    Released on J-STAGE: October 25, 2025
    Advance online publication: May 22, 2025
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    This study aimed to evaluate the effects of remote symptom monitoring (RSM) combined with progressive muscle relaxation (PMR) in lung cancer patients undergoing chemotherapy. A total of 134 lung cancer patients were recruited and randomly assigned to either the RSM + PMR group (n = 67) or the control group (n = 67). Assessments were conducted at baseline (T0), after the first chemotherapy cycle (T1), and after the second cycle (T2). Outcomes included pain [Visual Analogue Scale (VAS)], sleep quality [Pittsburgh Sleep Quality Index (PSQI)], anxiety and depression [Hospital Anxiety and Depression Scale (HADS)], and health-related quality of life (HRQoL, EORTC QLQ-C30). The RSM + PMR group demonstrated significant improvements compared to the control group in reducing pain, enhancing sleep quality, lower anxiety and depression scores at T1 and T2. In terms of HRQoL, the RSM + PMR group showed significant reductions in fatigue, pain, and nausea/vomiting, along with improvements in physical function, role functioning, and social functioning at T1. These positive effects persisted and even strengthened by T2, with further significant improvements in fatigue, pain, dyspnea, and nausea/vomiting. Additionally, the RSM + PMR group reported better global health status at both T1 and T2. By the end of the study (T2), patient satisfaction with the RSM + PMR intervention was significantly higher than in the control group. The RSM + PMR intervention effectively improved pain, sleep, anxiety, depression, and HRQoL in lung cancer patients during chemotherapy, offering a valuable strategy for symptom management.

  • Takehiro Sato, Masaki Miyasaka, Norio Tada, Tomoya Kobayashi, Mie Saku ...
    Article type: Regular Contribution
    2025Volume 267Issue 2 Pages 235-243
    Published: 2025
    Released on J-STAGE: October 25, 2025
    Advance online publication: November 07, 2024
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    The purpose of this retrospective study is to investigate the feasibility of measurement of aortic annular size using a respiratory and non-contrast magnetic resonance angiography (MRA) in comparison to those of computed tomography angiography (CTA) in an unselected, consecutive cohort of patients evaluated for transcatheter aortic valve replacement (TAVR). Of 295 consecutive patients (mean age 83.0 ± 4.5 years) with severe aortic stenosis, 68 underwent pre-TAVR CTA and a non-contrast balanced steady-state free precession MRA at 1.5 T. This study evaluated potential discrepancies in preoperative assessments of TAVR device size selection determined by CTA and MRA, and compared with paravalvular aortic valve regurgitation (PAR). The aortic annulus area (AAA) and perimeter (AAP) measured with systolic MRA showed a higher correlation to systolic CTA than those measured with diastolic MRA: intraclass correlation coefficient (ICC) with 95% concordance index (CI) of measured AAA between systolic CTA vs. systolic and diastolic MRA, 0.891 (CI 0.830-0.932) and 0.833 (CI 0.742-0.893), respectively; ICC with 95% CI of measured AVP between systolic CTA vs. systolic and diastolic MRA, 0.892 (CI 0.831-0.932) and 0.841 (CI 0.754-0.899). Of the 68 patients, 52 assigned the same device size, 2 assigned an oversized device, and 14 assigned undersized devices when sizing was based on systolic MRA as compared to systolic CTA. Virtual MRA-sizing assigned under-sizing for 14 patients, 9 of whom presented PAR grade 1 by CTA-sizing. This under-sizing could potentially increase the severity of PAR postoperatively, with the possibility of escalating PAR to grade 2 or above.

  • Qiwei Du, Minghe Zhang, Yuqing Huang, Ziqiang Wang, Nian Liu, Rongguo ...
    Article type: Regular Contribution
    2025Volume 267Issue 2 Pages 245-254
    Published: 2025
    Released on J-STAGE: October 29, 2025
    Advance online publication: March 27, 2025
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    Supplementary material

    Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, a subtype of which is papillary thyroid microcarcinoma (PTMC). Tenascin C (TNC) is associated with the proliferation and metastasis of medullary thyroid cancer cells. Accordingly, this work was attempted to explore the role of TNC in quantitative real-time PCR (qRT-PCR). The pathological data of PTMC patients were recorded and analyzed. A transplant tumor mouse model was established using TPC-1 cells. The tumor volume and weight were documented, and the cells in the tumor tissues were isolated and cultured. The expressions of E-cadherin, Vimentin, and TNC in the tumor tissues, TPC-1 cells, and tumor cells were determined using qRT-PCR, Western blot, and immunohistochemistry. The viability, invasion, and migration of thyroid cells, PTC cells, and mouse tumor cells were further examined. TNC was upregulated in the serum of PTMC patients and PTC cells. PTMC patients with a higher level (≥ median) of TNC had more obvious lymph node metastasis and more severe tumor node metastasis (TNM) stage. TNC overexpression increased the viability, invasion, migration and Vimentin expression, while decreasing E-cadherin level in thyroid cells and PTC cells. TNC silencing reduced the tumor volume and weight, upregulated E-cadherin level in tumors, and also inhibited the viability, invasion, and migration of tumor cells. This work found that TNC enhances the development of PTC and serves as a promising diagnostic biomarker in PTMC.

  • Jiao Wu, Tanwei Wei, Sha Zheng, Mei Long, Yi Chen, Yongguang Yuan
    Article type: Regular Contribution
    2025Volume 267Issue 2 Pages 255-262
    Published: 2025
    Released on J-STAGE: October 29, 2025
    Advance online publication: May 22, 2025
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    Supplementary material

    This article aimed to study the molecular mechanism of diabetic retinopathy (DR) and find new targets for the treatment of DR. IL1RN and hsa-miR-485-3p were screened the key molecules using bioinformatics means. Western blot or RT-qPCR results showed a high expression of hsa-miR-485-3p and a low IL1RN expression in high glucose (HG)-treated human retinal endothelial cells (HRECs) and DR patients. The dual luciferase reporter assay verified the targeting relationship of hsa-miR-485-3p to IL1RN, and up-regulating hsa-miR-485-3p hindered IL1RN expression. The Annexin-V/PI and transepithelial electrical resistance (TEER) assay displayed that HG induced HREC apoptosis and broke the tight connection function between cells. These effects of HG on HRECs were exacerbated by hsa-miR-485-3p upregulation and were attenuated by IL1RN overexpression. The receiver operating characteristic (ROC) curve and binary logistic regression analysis showed that hsa-miR-485-3p was a risk for progression to DR in patients with type 2 diabetes mellitus (T2DM), while IL1RN was a potential protective factor. In a word, hsa-miR-485-3p was involved in the development of DR by regulating IL1RN, and they have certain diagnostic value, indicating that they may be novel biomarkers of DR.

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