Biomedical research (Tokyo, Japan)最新文献

The distinct effect between Amyloid β (1‒40) and Amyloid β (1‒42) on the TRAP-stimulated platelet activation in diabetes mellitus. β淀粉样蛋白（1-40）和β淀粉样蛋白（1-42）对trap刺激的糖尿病血小板活化的不同影响。

Biomedical research (Tokyo, Japan) Pub Date : 2025-01-01 DOI: 10.2220/biomedres.46.119

Takuya Omura, Chika Usui, Rie Matsushima-Nishiwaki, Osamu Kozawa, Haruhiko Tokuda

{"title":"The distinct effect between Amyloid β (1‒40) and Amyloid β (1‒42) on the TRAP-stimulated platelet activation in diabetes mellitus.","authors":"Takuya Omura, Chika Usui, Rie Matsushima-Nishiwaki, Osamu Kozawa, Haruhiko Tokuda","doi":"10.2220/biomedres.46.119","DOIUrl":"https://doi.org/10.2220/biomedres.46.119","url":null,"abstract":"Amyloid β (Aβ) (1‒40) is the major form in amyloid plaques, while Aβ (1‒42) is predominant in neuronal plaques. Anti-Aβ antibodies are clinically accepted for Alzheimer's disease treatment to remove Aβ from neuronal plaques; however, increase of intracranial hemorrhagic risk is a major concern. We reported that Aβ (1‒40) inhibits thrombin receptor-activating protein (TRAP)-induced platelet activation in healthy volunteers, and the responsiveness of Aβ (1‒40) to the platelet activation is related to brain atrophy in diabetes mellitus (DM) patients. We investigated the difference between the effects of Aβ (1‒40) and Aβ (1‒42) on the platelet activation in DM participants. Both isoforms suppressed the platelet aggregation, but the effect of Aβ (1‒42) was smaller than Aβ (1‒40). The effect of Aβ (1‒42) on the TRAP-stimulated phosphorylation of p38 mitogen-activated protein kinase and stress-activated protein kinase/c-Jun N-terminal kinase was smaller than Aβ (1‒40). Although the differences were not clarified, the effective ratio of Aβ (1‒40) to Aβ (1‒42) on the PDGF-AB secretion effect was related to the ratio on the aggregation and the phosphorylated-HSP27 secretion. These results suggest that the difference of the effects exists between Aβ (1‒40) and Aβ (1‒42) on the TRAP-stimulated platelet activation individually in the DM patients.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"46 3","pages":"119-128"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Finerenone alleviates the high glucose-induced fibrosis in HK-2 cells by inhibiting EMT via the TGF-β1/Smads signaling. 芬烯酮通过TGF-β1/Smads信号抑制EMT，缓解高糖诱导的HK-2细胞纤维化。

Biomedical research (Tokyo, Japan) Pub Date : 2025-01-01 DOI: 10.2220/biomedres.46.83

Yanqiao Wang, Qiuyue Liu, Zili Zheng, Quanlin Zheng, Ruoji Chen, Shaoxin Zhang

{"title":"Finerenone alleviates the high glucose-induced fibrosis in HK-2 cells by inhibiting EMT via the TGF-β1/Smads signaling.","authors":"Yanqiao Wang, Qiuyue Liu, Zili Zheng, Quanlin Zheng, Ruoji Chen, Shaoxin Zhang","doi":"10.2220/biomedres.46.83","DOIUrl":"https://doi.org/10.2220/biomedres.46.83","url":null,"abstract":"Finerenone is a novel non-steroidal mineralocorticoid receptor antagonist and exhibits anti-fibrotic effects against diabetic nephropathy (DN), but its underlying mechanism of action remains unclear. This study aimed to elucidate the effects of Finerenone on high glucose (HG)-induced fibrosis in HK-2 cells and explore the underlying mechanisms. Finerenone was used to treat HG-stimulated HK-2 cells. ELISA and immunofluorescence assays were used to evaluate extracellular matrix (ECM) accumulation and epithelial-to-mesenchymal transition (EMT). Western blotting and molecular docking were performed to investigate the interaction of Finerenone with TGF-β1/Smad signaling. ALK5 knockdown experiments were conducted to confirm Finerenone's target specificity. Finerenone significantly reduced HG-induced fibronectin, collagen III, collagen IV and α-SMA expression. Moreover, Finerenone restored E-cadherin while suppressed N-cadherin and vimentin levels. Notably, it did not alter TGF-β1 production, but inhibited Smad2/3 phosphorylation. Molecular docking showed its competitively binding site to TGF-βR1, knockdown of which abolished Finerenone's anti-fibrotic effects. Finerenone mitigates HG-induced fibrosis in HK-2 cells by targeting TGF-βR1 and inhibiting downstream Smad signaling to modulate ECM accumulation and EMT. These findings provided mechanistic insights into Finerenone's potential as a therapeutic agent for DN.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"46 3","pages":"83-92"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The balance among radiation-induced cell death pathways in the p53-mutant human glioblastoma cell line T98G: A preliminary study. p53突变型人胶质母细胞瘤细胞系T98G中辐射诱导细胞死亡通路的平衡：初步研究

Biomedical research (Tokyo, Japan) Pub Date : 2025-01-01 DOI: 10.2220/biomedres.46.101

Hisashi Nakano, Juri Kidachi, Mitsuki Imazato, Mizuki Kojima, Kaori Tsutsumi

{"title":"The balance among radiation-induced cell death pathways in the p53-mutant human glioblastoma cell line T98G: A preliminary study.","authors":"Hisashi Nakano, Juri Kidachi, Mitsuki Imazato, Mizuki Kojima, Kaori Tsutsumi","doi":"10.2220/biomedres.46.101","DOIUrl":"https://doi.org/10.2220/biomedres.46.101","url":null,"abstract":"The specific contributions of apoptosis, necrosis, autophagy, and cellular senescence pathways in malignant tumor cells (especially p-53 defective or mutated tumors) are unclear. We evaluated the cell viability, apoptosis, autophagic cell death, and cell senescence of T98G cells irradiated with 6 megavoltage (MV) X-rays at 0, 2, 4, and 8 Gy. The cell-death rate obtained by a colony formation assay was used to derive the cell-surviving fraction at each irradiation dose. We evaluated the relative balance between each irradiation dose and the cell-death pathway by a four-dimensional (4D) plot generated by incorporating the cell-death rate, autophagic cell death, and cell senescence. A dose-dependent decrease in the cell-survival rate was observed, with no significant apoptosis induction at any dose. Autophagic cell death and cellular senescence both exhibited dose-dependent increases, with autophagy dominating at 2-4 Gy and senescence more prominent at 8 Gy. The complex relationships among apoptosis, autophagy, and senescence in T98G remain unresolved. Our results highlight the dose-dependent shifts in autophagy and senescence, providing a foundational understanding of cell-death dynamics in radiation-resistant tumors and perhaps paving the way for novel strategies that exploit these pathways to enhance glioblastoma treatments' efficacy.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"46 3","pages":"101-110"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Age-dependent changes of the perineuronal net in the mouse basal ganglia nuclei. 小鼠基底神经节核神经元周围网的年龄依赖性变化。

Biomedical research (Tokyo, Japan) Pub Date : 2025-01-01 DOI: 10.2220/biomedres.46.155

Fuyuki Karube, Linsen Lu, Fumino Fujiyama

{"title":"Age-dependent changes of the perineuronal net in the mouse basal ganglia nuclei.","authors":"Fuyuki Karube, Linsen Lu, Fumino Fujiyama","doi":"10.2220/biomedres.46.155","DOIUrl":"https://doi.org/10.2220/biomedres.46.155","url":null,"abstract":"Aging promotes mild but progressive decline of motor behaviors and cognitive functions, related to loss of plasticity. Recovery of neural plasticity may become a possible clinical treatment against aging. Perineuronal net (PNN) is the extracellular matrix surrounding cell bodies of neurons, and is known to affect plasticity and survival of neurons. The basal ganglia are motor-related regions of the brain, and earlier reports revealed that neurons in the output nuclei of the basal ganglia form PNN. However, the detailed characteristics are not fully clarified yet. We found intensive PNN expression in the entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr). PNN surrounded parvalbumin-expressing large axon terminals in the EP and SNr. The proportion of PNN-forming neurons was lower in young mice, and gradually increased with age. The fluorescent intensity of PNN showed similar changes in the EP and SNr. We also showed that the motor ability examined by the rotarod test correlated with PNN expression in the SNr. It may provide the possibility of PNN modulation to improve plasticity and quality of behaviors in aged animals.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"46 4","pages":"155-166"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Methionine oxidation of TRPV2 regulates thermogenesis in brown adipocytes. TRPV2的蛋氨酸氧化调节棕色脂肪细胞的产热。

Biomedical research (Tokyo, Japan) Pub Date : 2025-01-01 DOI: 10.2220/biomedres.46.145

Mari Iwase, Satoko Kawarasaki, Tsuyoshi Goto, Kunitoshi Uchida

{"title":"Methionine oxidation of TRPV2 regulates thermogenesis in brown adipocytes.","authors":"Mari Iwase, Satoko Kawarasaki, Tsuyoshi Goto, Kunitoshi Uchida","doi":"10.2220/biomedres.46.145","DOIUrl":"https://doi.org/10.2220/biomedres.46.145","url":null,"abstract":"Transient receptor potential vanilloid 2 (TRPV2) is a non-selective cation channel activated by mechanical stimuli and temperatures above 52°C. Although we have previously reported that TRPV2 regulates non-shivering thermogenesis through facilitating the expression of genes related to thermogenesis, how TRPV2 activity is regulated in brown adipocytes under physiological conditions remains unclear. Recently, methionine oxidation was reported to lower the activation temperature threshold of TRPV2 to around or even below core body temperature. In the present study, we investigated whether methionine oxidation activates TRPV2 and regulates thermogenesis in the differentiated brown adipocytes. As a result, treatment with Chloramine-T (ChT, a methionine oxidant) activated TRPV2 at temperatures of >30°C in mouse TRPV2-expressing HEK293T cells and in the differentiated brown adipocytes. Moreover, ChT treatment enhanced the expression of genes related to thermogenesis in the differentiated brown adipocytes. These results suggest that methionine oxidation might activate TRPV2 at around body temperature and increase thermogenesis-related gene expression.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"46 4","pages":"145-153"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multihormone-producing capabilities of normal pancreatic islet cells-spatial transcriptomics analysis using Xenium. 正常胰岛细胞的多激素产生能力-使用Xenium进行空间转录组学分析。

Biomedical research (Tokyo, Japan) Pub Date : 2025-01-01 DOI: 10.2220/biomedres.46.129

Akane Naruoka, Ken Yamaguchi, Takashi Sugino, Keiichi Hatakeyama, Keiichi Ohshima, Takeshi Nagashima, Koji Muramatsu, Teiichi Sugiura, Katsuhiko Uesaka, Kenichi Urakami, Yasuto Akiyama

{"title":"Multihormone-producing capabilities of normal pancreatic islet cells-spatial transcriptomics analysis using Xenium.","authors":"Akane Naruoka, Ken Yamaguchi, Takashi Sugino, Keiichi Hatakeyama, Keiichi Ohshima, Takeshi Nagashima, Koji Muramatsu, Teiichi Sugiura, Katsuhiko Uesaka, Kenichi Urakami, Yasuto Akiyama","doi":"10.2220/biomedres.46.129","DOIUrl":"https://doi.org/10.2220/biomedres.46.129","url":null,"abstract":"The aim of this study is to clarify whether adult pancreatic islet cells would strictly maintain the ability to produce a single pancreatic hormone, or whether they would retain the plasticity to produce two or more pancreatic hormones simultaneously. The ability to produce pancreatic hormones was estimated by the number of hormone gene transcripts, which was evaluated by a spatial transcriptomics analysis using Xenium. The spatial analysis was performed using 477 probes on pancreatic tissues surgically removed from three patients with pancreatic tumors. Eleven pancreatic islets were selected from pancreatic tissue sections, and a detailed analysis was performed on the number of glucagon, insulin, somatostatin and pancreatic polypeptide gene transcripts in the total of 773 pancreatic islet cells. The spatial analysis revealed that a large number of pancreatic islet cells possessed multiple gene transcripts of four pancreatic hormones. Based on these results, as far as gene expression is concerned, it is possible to speculate that adult pancreatic islet cells have the plasticity to produce two or more pancreatic hormones simultaneously. These results suggested that the hormone-producing capabilities of the conventional A, B, D and PP pancreatic islet cells would need to be re-examined.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"46 3","pages":"129-136"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disturbance on drug efficacy of dapagliflozin, an SGLT2 inhibitor, in mice. SGLT2抑制剂达格列净对小鼠药效的影响。

Biomedical research (Tokyo, Japan) Pub Date : 2025-01-01 DOI: 10.2220/biomedres.46.137

Hiroki Yoshioka, Fumiya Amano, Aiko Yano, Kenichi Ogata, Shuji Yamashita, Aya Torii-Goto, Hirotaka Yamashita, Naoki Inagaki, Nobuhiko Miura, Hyogo Horiguchi, Masae Yoshikawa

{"title":"Disturbance on drug efficacy of dapagliflozin, an SGLT2 inhibitor, in mice.","authors":"Hiroki Yoshioka, Fumiya Amano, Aiko Yano, Kenichi Ogata, Shuji Yamashita, Aya Torii-Goto, Hirotaka Yamashita, Naoki Inagaki, Nobuhiko Miura, Hyogo Horiguchi, Masae Yoshikawa","doi":"10.2220/biomedres.46.137","DOIUrl":"https://doi.org/10.2220/biomedres.46.137","url":null,"abstract":"This study aimed to investigate the efficacy of dapagliflozin administration time using light-dark cycle-disrupted mice. Five-week-old male C57BL/6J mice were fed a control diet or high-fat diet (HFD) for 8-weeks under a disrupted light-dark cycle. During the final 2-weeks of the study, the mice were administered dapagliflozin at a fixed time (8:00) or 2-h after the light phase, respectively. An olive oil-ethanol emulsion was used as the vehicle. At the end of the experiment, the mice were euthanized after an 18-hour fasting period, and plasma and tissue samples (epididymal white adipose tissue, liver, and kidney) were collected. Dapagliflozin administration significantly reduced the HFD-induced body weight gain in both treatment groups. However, the effect of dapagliflozin on body weight reduction was stronger at a fixed time than 2-h after the disrupted light phase. In addition, the administration of dapagliflozin at a fixed time significantly decreased HFD-induced affects such as hyperglycemia and hyperinsulinemia. Although dapagliflozin administration 2-h after the light phase tended to be effective, the levels were lower than those at the fixed time. Our findings suggest that the time to take medicines such as dapagliflozin in shift workers should be fixed at a regular time rather than after waking up.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"46 4","pages":"137-144"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The translocator protein ligand Ro5-4864 inhibits RANKL-induced osteoclastogenesis in mice. 转运蛋白配体Ro5-4864抑制rankl诱导的小鼠破骨细胞生成。

Biomedical research (Tokyo, Japan) Pub Date : 2025-01-01 DOI: 10.2220/biomedres.46.167

Nobutaka Matsuura, Kazuyoshi Takeda, Yuka Sendai, Tatsuya Ichinohe, Nobuyuki Matsuura, Toshifumi Azuma, Ko Okumura, Tatsukuni Ohno

{"title":"The translocator protein ligand Ro5-4864 inhibits RANKL-induced osteoclastogenesis in mice.","authors":"Nobutaka Matsuura, Kazuyoshi Takeda, Yuka Sendai, Tatsuya Ichinohe, Nobuyuki Matsuura, Toshifumi Azuma, Ko Okumura, Tatsukuni Ohno","doi":"10.2220/biomedres.46.167","DOIUrl":"https://doi.org/10.2220/biomedres.46.167","url":null,"abstract":"The translocator protein (TSPO) is a mitochondrial outer membrane protein that is constitutively expressed in various immune cells, including macrophages, dendritic cells, T cells, and B cells. TSPO has been implicated in mitochondrial function and immune regulation, particularly in macrophages, which are also osteoclast precursors. However, its role in osteoclast differentiation remains unclear. This study examined the effects of the TSPO ligand Ro5-4864 on osteoclast differentiation using murine bone marrow-derived macrophages (BMMs) and the RAW 264.7 macrophage cell line. TSPO was confirmed to be expressed constitutively in BMMs and remained detectable after stimulation with receptor activator of NF-κB ligand (RANKL), consistent with a potential role in osteoclastogenesis. Treatment with Ro5-4864 suppressed RANKL-induced osteoclast differentiation in both BMMs and RAW264.7 cells. This suppression of osteoclast differentiation was accompanied by downregulation of osteoclast-associated genes, including Nfatc1, Acp5, Mmp9, and Ctsk. Metabolic analysis revealed that Ro5-4864 decreased cellular ATP levels without altering lactate production. Ro5-4864 also increased the mitochondrial membrane potential. Although the specific role of TSPO in osteoclastogenesis remains unclear, our findings suggest that Ro5-4864 inhibits osteoclast differentiation via mechanisms related to TSPO and mitochondrial energy metabolism.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"46 4","pages":"167-176"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pro-gastrin-releasing peptide expression in Ewing sarcoma cells in vitro and in vivo demonstrates its availability as a valuable tumor marker. 前胃泌素释放肽在体外和体内尤因肉瘤细胞中的表达证明了其作为一种有价值的肿瘤标志物的有效性。

Biomedical research (Tokyo, Japan) Pub Date : 2025-01-01 DOI: 10.2220/biomedres.46.111

Kouji Maruyama, Koji Muramatsu, Hidee Ishii, Yu Takahashi, Naoki Sakura, Keiichi Hatakeyama, Tohru Mochizuki, Keiichi Ohshima, Takashi Nagashima, Yoji Hirabayashi, Shumpei Ohnami, Sumiko Ohnami, Takashi Sugino, Mitsuru Takahashi, Hirohisa Katagiri, Kenichi Urakami, Yasuto Akiyama, Ken Yamaguchi

{"title":"Pro-gastrin-releasing peptide expression in Ewing sarcoma cells in vitro and in vivo demonstrates its availability as a valuable tumor marker.","authors":"Kouji Maruyama, Koji Muramatsu, Hidee Ishii, Yu Takahashi, Naoki Sakura, Keiichi Hatakeyama, Tohru Mochizuki, Keiichi Ohshima, Takashi Nagashima, Yoji Hirabayashi, Shumpei Ohnami, Sumiko Ohnami, Takashi Sugino, Mitsuru Takahashi, Hirohisa Katagiri, Kenichi Urakami, Yasuto Akiyama, Ken Yamaguchi","doi":"10.2220/biomedres.46.111","DOIUrl":"https://doi.org/10.2220/biomedres.46.111","url":null,"abstract":"Pro-gastrin-releasing peptide (ProGRP) is the precursor of gastrin-releasing peptide (GRP), a neuropeptide hormone with diverse biological activities. ProGRP is an established tumor marker for small cell lung carcinoma (SCLC). Recently, we reported the usefulness of ProGRP as a tumor marker for Ewing's sarcoma (ES) family tumors (ESFTs). We performed in vitro and in vivo studies on the expression of ProGRP in ES cell lines to assess the reliability of ProGRP as a tumor marker for ESFTs. High levels of GRP mRNA and ProGRP protein were detected in ES cell lines, including A-673, SK-N-MC, SK-NEP-1, and DMS 53 SCLC cell line, but no expression was detected in SU-CCS-1 clear cell sarcoma cell line. ProGRP expression was also detected in in vivo studies using tumor-bearing athymic mice inoculated with ES and SCLC cell lines. In tumor growth experiment using A-673 cells, plasma ProGRP was detected in all mice one week after tumor cell inoculation. Plasma ProGRP levels increased with increasing tumor size, and surgical resection of the tumor on Day 21 eliminated plasma ProGRP completely. These results demonstrate that ProGRP is produced and released by ES cells and strongly indicate the high ability of ProGRP as a diagnostic marker for ESFTs.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"46 3","pages":"111-118"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Remimazolam and dexmedetomidine prevent cognitive decline by affecting lipopolysaccharide-induced brain injury in mice: Possible involvement of the vagus nerve pathway. 雷马唑仑和右美托咪定通过影响脂多糖诱导的小鼠脑损伤来预防认知能力下降：可能涉及迷走神经通路。

Biomedical research (Tokyo, Japan) Pub Date : 2025-01-01 DOI: 10.2220/biomedres.46.177

Wei Wang, Yosuke Uchida, Yuji Morimoto

{"title":"Remimazolam and dexmedetomidine prevent cognitive decline by affecting lipopolysaccharide-induced brain injury in mice: Possible involvement of the vagus nerve pathway.","authors":"Wei Wang, Yosuke Uchida, Yuji Morimoto","doi":"10.2220/biomedres.46.177","DOIUrl":"https://doi.org/10.2220/biomedres.46.177","url":null,"abstract":"Sepsis-associated encephalopathy (SAE) is a critical neurological complication of sepsis with limited therapeutic options. This study investigated the neuroprotective potential of remimazolam (REMI) and dexmedetomidine (DEX) in a lipopolysaccharide (LPS)-induced murine model of SAE. We assessed cognitive function via trace fear conditioning, hippocampal CA3 neuronal integrity, neuroinflammatory markers (TNF-α, IL-6, IL-1β), blood-brain barrier (BBB) permeability through hippocampal albumin levels, and lung Netrin-1 expression as an indicator of vagus nerve pathway activity. LPS administration resulted in significant cognitive deficits, CA3 neuronal damage, elevated systemic and central pro-inflammatory cytokines, increased BBB permeability, and reduced lung Netrin-1. Pre-treatment with either REMI or DEX substantially ameliorated these LPS-induced neuropathological changes and cognitive impairments. Notably, the protective effects of both agents on cognitive function were significantly attenuated by the α7 nicotinic acetylcholine receptor (α7nAChR) antagonist, methyllycaconitine. These findings suggest that REMI and DEX exert neuroprotective effects against LPS-induced acute brain injury and cognitive decline, likely mediated, at least in part, through the α7nAChR pathway, highlighting their potential therapeutic relevance in mitigating SAE.","PeriodicalId":520570,"journal":{"name":"Biomedical research (Tokyo, Japan)","volume":"46 4","pages":"177-187"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0