Tohoku Journal of Experimental Medicine最新文献

Chemotherapy options for patients with advanced esophageal cancer had been limited until immune checkpoint inhibitors (ICIs) were approved for this indication. In recent years, ICI alone and ICI-combined chemotherapy have been approved, which prolonged the overall survival (OS) of patients with advanced esophageal cancer. We retrospectively analyzed 265 patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) who received chemotherapy with and without ICIs at Tohoku University Hospital from January 2013 to March 2022. Cisplatin plus fluorouracil therapy was the most frequently administered regimen as first-line treatment, and their administration frequency did not significantly differ between before 2019 and after 2020. Nivolumab was the most frequently used treatment as second-line therapy since its first approval in 2020 (74%), whereas taxanes were the most frequently used regimen before 2019 (55%). The median OS was 13.9 months over the entire observation period. Among patients who received second-line therapy, those receiving ICIs at any line demonstrated significantly longer OS from the start of second-line treatment than the others (p = 0.03). Univariate analysis revealed that a G8 score of < 11 (hazard ratio: 1.62, p = 0.02) was a prognostic factor in patients aged ≥ 65 years. Among each components of the G8 score, a decrease in food intake, weight loss, impaired mobility, and self-perceived poor health status were shown to be particularly associated with shorter OS. Our real-world data demonstrated that ICI administration contributed to improved OS after initiating second-line treatment for unresectable, advanced, or recurrent ESCC. Additionally, we revealed that the G8 score could be a useful prognostic factor in elderly patients with advanced ESCC treated with chemotherapy.

We aimed to investigate the glaucoma-detecting ability of MEOCHECK, a novel and simple visual field measurement device based on retinal projection technology. This retrospective and observational study evaluated 94 glaucomatous eyes of 49 subjects and 31 non-glaucomatous eyes of 23 healthy subjects. We compared MEOCHECK's main output, Score 100, to visual acuity, intraocular pressure, optical coherence tomography-measured parameters (circumpapillary retinal nerve fiber layer thickness [cpRNFLT] and ganglion cell complex thickness [GCCT]), and automated perimetry-measured mean deviation (MD) in glaucomatous eyes. Score 100 showed significant correlations with age, visual acuity, cpRNFLT, GCCT, and MD (r = --0.38, p < 0.001; r = -0.42, p < 0.001; r = 0.65, p < 0.001; r = 0.59, p < 0.001; and r = 0.62, p < 0.001, respectively). Score 100 was statistically significantly lower in early- vs. moderate-stage glaucoma (p = 0.03) and in moderate- vs. severe-stage glaucoma (p = 0.002). A logistic regression analysis indicated that Score 100 could predict the presence of glaucoma, with an area under the receiver operating characteristic curve of 0.89. MEOCHECK, a novel device that uses retinal projection technology, effectively detected glaucomatous visual fields, demonstrating its potential as a reliable tool for glaucoma detection.

The infection of Enterovirus A 71 (EV-A71) could cause severe hand-foot-mouth disease (HFMD), which poses a grave threat to the lives of children. Moreover, in some cases where the children survive, long-term neurological sequelae may occur. Acupuncture can alleviate cognitive dysfunction, however, its role in HFMD has not been investigated. HFMD models caused by EV-A71 infection were constructed in Sprague-Dawley infant rats. Morris water maze test was employed to evaluate the spatial learning and memory function administered by the interventions of SB203580 or/and acupuncture. The changes and apoptosis degree of hippocampus tissues were evaluated by H&E staining and TUNEL staining assay. Furthermore, the western blot was utilized to detect the apoptosis-related proteins as well as the proteins involved in the p38 MAPK/CREB pathway within the tissues. After induction with EV-A71, compared to the control group, the rat's escape latency increased noticeably, while the time duration spent on the platform and the number of platform-crossing times decreased significantly. Moreover, in the hippocampal tissues of EV-A71-infected rats, pyramidal cells were loosely arranged, of different sizes and disorganized, as well as the numbers of neuronal cell apoptosis were significantly elevated, accompanied by increased expression of phosphorylated p38 and down-regulations of phosphorylated CREB. Interestingly, these effects could be relieved by acupuncture or SB203580 intervention, and acupuncture could additionally enhance the influence of SB203580. Acupuncture might modulate the p38 MAPK/CREB pathway, thus alleviating the impairment of spatial learning and memory, as well as the apoptosis in the hippocampus of rats infected with EV-A71.

Reprogramming of glucose metabolism is a hallmark of hepatocellular carcinoma (HCC); however, the intrinsic mechanisms underlying this phenomenon remain unclear. The present study aimed to investigate the role and potential mechanism of glycyl-tRNA synthetase (GARS) in HCC glycolysis. Our results revealed an increase in the expression of Kruppel-like factor 16 (KLF16) and forkhead box K1 (FOXK1) in HCC tissues and correlated with an unfavorable prognosis. Mechanistically, we demonstrated that KLF16 binds to the promoter region of GARS, thereby enhancing its transcription. Subsequently, the GARS protein then binds to FOXK1, resulting in reduced ubiquitination and increased stability of FOXK1. FOXK1 then promotes glycolysis by directly stimulating the transcription of lactate dehydrogenase A, pyruvate kinase M2 and glucose transporter 1 in HCC cells. Additionally, KLF16 knockdown inhibited glycolysis in HCCLM3 cells both in vitro and in vivo. Collectively, these findings indicate that the KLF16-GARS-FOXK1 axis plays a critical role in regulating HCC growth and glycolysis. Targeting this pathway may hold a promising therapeutic strategy for HCC treatment.

This study explores the regulatory effects of Heat Shock Protein A1B (HSPA1B) on gene expression related to blood pressure in Human Umbilical Vein Endothelial Cells (HUVECs) and delineates its underlying mechanisms. Given the global prevalence of hypertension as a major risk factor for cardiovascular and cerebrovascular diseases, understanding its molecular underpinnings is crucial. We utilized cloning, cell culture, RNA isolation, cDNA synthesis, PCR amplification, high-throughput sequencing, and alternative splicing analysis to evaluate the impact of HSPA1B overexpression on HUVECs. The findings revealed that HSPA1B overexpression leads to significant changes in gene expression and alternative splicing patterns, implicating various molecular pathways. Notably, genes associated with inflammation, immune response, apoptosis, and endothelial function were upregulated, while others were downregulated. These alterations suggest that HSPA1B may influence endothelial cell responses under stress conditions. This study provides insights into the molecular mechanisms that could contribute to hypertension development and identifies HSPA1B as a potential area for further research in therapeutic strategies to manage this condition.

Mobile radiography is useful for triaging patients during disasters. However, in the face of large-scale disasters, medical equipment, including X-ray systems, may be restricted because of power outages. Therefore, a novel mobile radiography system that can be used in any disaster was developed, and its basic performance was evaluated. This system is designed for use during power outages and can be recharged using both household and solar power sources. The reproducibility of the X-ray output of the system (irradiation dose, tube voltage, radiation quality and irradiation time) was excellent, confirming that radiography could be performed consistently. The entrance surface dose and scattered radiation during chest radiography were measured using a chest phantom. Both results were acceptable, verifying that the system is sufficiently safe from the viewpoint of radiation protection. This novel mobile radiology system is easy to carry and can generate solar power, making it useful during a power outage in the case of a large-scale disaster or when examinations need to be performed outside a hospital, such as at a first-aid station.