Tohoku Journal of Experimental Medicine最新文献

The vulnerability of carotid plaque is a risk factor for the development of acute cerebral infarction (ACI). Contrast-enhanced ultrasound (CEUS) is widely employed in the assessment of carotid plaque. miR-125b-5p was reported to be associated with the development of ACI. The aim was to investigate the diagnostic value of CEUS combined with serum miR-125b-5p for ACI and its correlation with carotid plaque. The study included 102 ACI patients and 80 non-ACI patients (controls) with carotid plaques. All subjects underwent CEUS examination. Serum miR-125b-5p levels were detected by RT-qPCR. The correlation between plaque neovascularization grade and each indicator was analyzed by Spearman's method. The diagnostic value of CEUS combined with miR-125b-5p was analyzed by the ROC curve. CEUS parameters peak intensity ratio (PIR) and area under the curve (AUC_ceus) values were higher in the ACI group, but mean transit time (MTT) and time to peak (TTP) values were significantly lower. In ACI patients, miR-125b-5p was upregulated and positively correlated with NIHSS scores. The combination of miR-125b-5p, TTP, and AUC_ceus showed higher AUC, sensitivity, and specificity than the individual indicators in differentiating between ACI patients and controls. PIR, TTP, AUC_ceus, MTT, and miR-125b-5p were strongly correlated with neovascularization grades of ACI patients. The combination of CEUS with serum miR-125b-5p had better diagnostic significance in ACI patients with carotid plaque. CEUS parameters and serum miR-125b-5p were significantly correlated with carotid plaque neovascularization.

Diabetic retinopathy (DR) is a critical and prevalent microvascular complication in patients with diabetes mellitus (DM), potentially culminating in blindness. Although lncRNA HCG11 has been proposed as a biomarker for this type of disease, supporting evidence remains sparse. This research endeavor is aimed at explicating the clinical relevance and molecular underpinnings of lncRNA HCG11 in DR patients. Serum levels of HCG11 were quantified in both DR and DM patients to assess its potential as an early diagnostic biomarker. Additionally, the effects of HCG11 on human retinal pigment epithelial cells (ARPE-19) were investigated in a vitro cell model, and the interaction between HCG11 and miR-532-3p was investigated through a dual-luciferase reporter assay. The results indicated that a significant upregulation of HCG11 in DR patients and could distinguish DR patients from those with DM with high sensitivity and specificity. In vitro experiments revealed that knockdown of HCG11 mitigated high glucose-induced inhibition of cell viability, reduced apoptosis, and lowered inflammatory cytokine secretion. The dual-luciferase reporter assay confirmed the binding interaction between HCG11 and miR-532-3p, also noting a negative correlation. The detailed mechanisms of their interaction warrant further investigation. lncRNA HCG11 was pivotal in the pathogenesis of DR, emerging as a promising diagnostic and therapeutic target. This study offers novel molecular insights and potential strategies for diagnosing and treating diabetic retinopathy.

Vascular endothelial dysfunction plays a critical role in the development of preeclampsia (PE). Secreted protein acidic and cysteine rich like 1 (SPARCL1) plays a role in regulating angiogenesis, yet its role in PE remains unclear. This study investigates the involvement of SPARCL1 in the development of PE. Placental tissues from healthy volunteers and patients with PE were collected to detect the expression of SPARCL1. Human umbilical vein endothelial cells (HUVECs) cultured under hypoxic conditions were utilized to investigate the role of SPARCL1 in PE. The biological behaviors of the cells were examined through cell functional assay. The expressions of DLL4/NOTCH1/HES1/VEGF proteins as well as apoptosis-related proteins were evaluated by western blot. The effects of SPARCL1/DLL4 on hypoxia-induced HUVECs were verified via rescue experiments. SPARCL1 was upregulated in placental tissues of PE patients and hypoxia-induced HUVECs. In hypoxia-induced HUVECs, shSPARCL1 facilitated the proliferative, migratory, invasive, and tube-forming capabilities yet inhibited apoptosis. ShSPARCL1 upregulated the protein levels of VEGF, HES1, NOTCH1 and DLL4. However, above-mentioned effects were all reversed by shDLL4. SPARCL1 may influence the proliferative, migratory, invasive, and tube-forming capabilities of hypoxia-induced HUVECs by regulating the DLL4/NOTCH1 axis, thereby facilitating the progression of PE.

Septic lung injury is a severe clinical problem with high mortality, and oxidative stress plays a critical role in its pathogenesis. This research focused on investigating how IGF2BP3 stabilizes CCL25 mRNA and its subsequent effects on cellular oxidative stress and septic lung injury. An in vitro cell injury model was established using LPS. The CCK-8 assay, flow cytometry and ELISA were employed to evaluate cell viability, death and inflammatory cytokine levels respectively. ROS accumulation, MDA content and antioxidant enzyme activities (SOD and GSH-Px) were quantified. Analysis of IGF2BP3 and CCL25 expression was conducted through qPCR and Western Blot. To confirm the interaction between IGF2BP3 and CCL25 mRNA, RIP and RNA pull-down were conducted. CCL25 mRNA stability was assessed following actinomycin D administration. Sepsis-caused lung injury model was created using CLP in mice. Further validation of CCL25's involvement in septic lung injury was conducted through qPCR, Western Blot, HE, ELISA and measurement of oxidative stress indicators. After LPS treatment, the cell viability was significantly decreased and the cell death, inflammation as well as oxidative stress were induced, the expressions of IGF2BP3 as well as CCL25 were markedly increased. Knockdown of CCL25 alleviated cellular oxidative stress and cellular damage caused by LPS. In addition, IGF2BP3 bound CCL25 and stabilized CCL25 mRNA, thus regulating LPS-induced cellular oxidative stress and cellular damage. In vivo, knockdown of CCL25 alleviated oxidative stress and inflammatory injury of lung tissue. CCL25 stabilized by IGF2BP3 could promote septic lung injury by inducing cellular oxidative stress.

Allergic rhinitis (AR) is a highly prevalent, chronic hypersensitivity reaction of the nasal mucosa. The exact function of miR-20b-5p in AR is currently unknown. The purpose of this study was to investigate the relationship between miR-20b-5p and illness risk, as well as its function in AR. One hundred and seventy-six patients provided blood samples. Human nasal epithelial cells (NEPCs) stimulated with 50 ng/mL interleukin-13 (IL-13) created the in vitro research model of AR. A receiver operator characteristic (ROC) curve was used to illustrate the miR-20b-5p clinical predictive value. Cell transfection was used to regulate gene expression. By using qRT-PCR, the expression levels of signal transducer and activator of transcription 3 (STAT3) and miR-20b-5p were examined. The CCK-8 kit was used to measure cell viability. Using a flow cytometer, cell apoptosis was found. Enzyme-linked immunosorbent assay (ELISA) was used to investigate the serum IgE and the inflammatory evaluation, which included MUC5AC, eotaxin, GM-CSF. The dual luciferase reporter system was employed to confirm the targeting link between miR-20b-5p and STAT3. The relative miR-20b-5p level was diminished in AR patients, in addition to human NEPCs induced with IL-13. Up-regulation of miR-20b-5p inverted decreased cell viability and elevated cell apoptosis. Moreover, the content of inflammatory cytokines MUC5AC, eotaxin, and GM-CSF was strengthened after IL-13 treatment, and highly expressed miR-20b-5p restrained the levels of inflammation dramatically. ROC curves with high sensitivity and specificity suggested miR-20b-5p as a potential biomarker for illness prediction. STAT3 was a potential downstream target of miR-20b-5p. miR-20b-5p serves as a candidate biomarker for AR. Enhanced miR-20b-5p can inhibit nasal epithelial cell inflammation and apoptosis.

Vascular calcification (VC) represents a highly significant and independent risk factor associated with increased mortality in hemodialysis patients. This study aimed to investigate the potential clinical significance of microRNA (miR)-106a-5p in the pathogenesis of vascular VC. This study included 165 hemodialysis patients with VC and 90 hemodialysis patients without VC. The expression levels of miR-106a-5p were assessed using quantitative real-time polymerase chain reaction (RT-qPCR) technology. Serum parathyroid hormone (PTH) levels were determined via chemiluminescence immunoassay (CLIA), while osteocalcin levels were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, the diagnostic value of miR-106a-5p for VC was evaluated using receiver operating characteristic (ROC) curve analysis. Multivariate logistic regression analysis was employed to identify risk factors associated with VC. Advanced age, prolonged dialysis duration, elevated alkaline phosphatase levels, higher blood calcium concentrations, and increased inflammatory response [as indicated by higher C-reactive protein (CRP) levels] were potential risk factors for VC in dialysis patients. RT-qPCR revealed a significant reduction in miR-106a-5p expression in the VC patient group. Furthermore, as the severity of VC progressed from mild to moderate to severe, miR-106a-5p expression progressively decreased. Multivariate logistic regression analysis identified age, CRP, and miR-106a-5p as significant predictors of VC. Additionally, PTH and osteocalcin levels were significantly higher in the VC group, with miR-106a-5p expression negatively correlated with PTH and osteocalcin levels. ROC curve analysis demonstrated that miR-106a-5p has diagnostic utility for VC. In conclusion, miR-106a-5p held potential as a diagnostic marker in the process of VC.