Tohoku Journal of Experimental Medicine最新文献

Necrotizing enterocolitis (NEC) is a severe and damaging disorder of the gastrointestinal tract, primarily affecting premature babies. The study aimed to explore the clinical significance of miR-194-5p in NEC and elucidate its effect on lipopolysaccharides (LPS)-induced inflammatory response and oxidative stress. The expression level of miR-194-5p was detected by Real-time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR), and the clinical value of miR-194-5p was analyzed by Receiver Operating Characteristic (ROC) analysis and logistic regression analysis. In addition, the levels of inflammatory factors and markers of oxidative stress were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA) kit. Cell viability was measured by Cell Counting Kit-8 (CCK-8) and the targeting relationship between miR-194-5p and TNF receptor associated factor 6 (TRAF6) was evaluated by dual luciferase reporter gene assay. miR-194-5p was down-regulated in the serum of premature infants with NEC and had a diagnostic value on NEC. Meanwhile, miR-194-5p regulated LPS-induced inflammation and oxidative stress responses by targeting TRAF6. In conclusion, miR-194-5p inhibited the progression of NEC, and miR-194-5p may be a biomarker for premature infants with NEC.

The vasohibin (VASH) family includes vasohibin-1 (VASH1), whose expression is induced in vascular endothelial cells by angiogenic factors such as vascular endothelial growth factor (VEGF) to inhibit angiogenesis via a negative feedback loop, and vasohibin-2 (VASH2), a homolog of VASH1, which is mainly expressed in cancer cells and promotes angiogenesis. VASH proteins have been associated with tumor angiogenesis and prognosis in various tumor types, drawing attention to their role in tumor biology. To date, no studies have reported on the expression of VEGF, VASH1, and VASH2 in benign parotid gland tumors. Therefore, in this study, we aimed to investigate their expression in these tumors. Our cohort consisted of 28 patients with benign parotid gland tumors, aged 31-79 (mean age 60.0 ± 13.8) years. Tumors were histologically diagnosed as pleomorphic adenoma in 15 patients (15 specimens) and Warthin's tumor in 13 patients (15 specimens). Immunohistochemical staining for VEGF, VASH1, and VASH2 was assessed based on the percentage of stained cells per slide (0-100%) and staining intensity, quantified using the H score. Immunostaining for VEGF, VASH1, and VASH2 demonstrated that Warthin's tumors had statistically significantly higher H-scores compared to pleomorphic adenomas. In addition, CD31 immunostaining showed a higher mean microvessel density (MVD) in the tumor stroma in Warthin's tumors than in pleomorphic adenomas. Similarly, CD34 immunostaining showed a higher number of spindle cells in the tumor stroma in Warthin's tumors than in pleomorphic adenomas. These findings suggest that the overexpression of VEGF, VASH1, and VASH2 is likely involved in the pathogenesis of benign parotid gland tumors.

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.