Tohoku Journal of Experimental Medicine最新文献

Arteriosclerosis obliterans (ASO) is characterized by arterial narrowing and blockage due to atherosclerosis, influenced by endothelial dysfunction and inflammation. This research focuses on exploring the role of MAGOH-DT, a long noncoding RNA, in mediating endothelial cell dysfunction through endothelial-mesenchymal transition (EndMT) under inflammatory and hyperglycemic stimuli, aiming to uncover potential therapeutic targets for ASO. Differential expression of lncRNAs, including MAGOH-DT, was initially identified in arterial tissues from ASO patients compared to healthy controls through lncRNA microarray analysis. Validation of MAGOH-DT expression in response to tumor necrosis factor-alpha (TNF-α) and high glucose (HG) was performed in human umbilical vein endothelial cells (HUVECs) using RT-qPCR. The effects of MAGOH-DT and HNRPC knockdown on EndMT were assessed by evaluating EndMT markers and TGF-β2 protein expression with Western blot analysis. RNA-immunoprecipitation assays were used to explore the interaction between MAGOH-DT and HNRPC, focusing on their role in regulating TGF-β2 translation. In the results, MAGOH-DT expression is found to be upregulated in ASO and further induced in HUVECs under TNF-α/HG conditions, contributing to the facilitation of EndMT. Silencing MAGOH-DT or HNRPC is shown to inhibit the TNF-α/HG-induced increase in TGF-β2 protein expression, effectively attenuating EndMT processes without altering TGF-β2 mRNA levels. In conclusion, MAGOH-DT is identified as a key mediator in the process of TNF-α/HG-induced EndMT in ASO, offering a promising therapeutic target. Inhibition of MAGOH-DT presents a novel therapeutic strategy for ASO management, especially in cases complicated by diabetes mellitus. Further exploration into the therapeutic implications of MAGOH-DT modulation in ASO treatment is warranted.

Helicobacter pylori (H. pylori) plays an important role in chronic atrophic gastritis (CAG). Interestingly, Shaoyao Gancao decoction (SGD), a traditional Chinese analgesic prescription, has the efficacy of relaxing spasms and relieving pain. Here, we aimed to identify whether SGD alleviates CAG and the underlying mechanism. A CAG mouse model was developed using H. pylori colonization and a high-salt diet. Histological staining was used to study the histopathological damage changes, and RT-qPCR assays the production of inflammatory responses in the gastric mucosa of mice. H. pylori and a high-salt diet induced gastric mucosal damage and apoptosis of gastric mucosal epithelial cells in mice, eliciting a significant inflammatory response. Treatment with SGD alleviated CAG-induced gastric mucosal damage, reduced apoptosis of gastric mucosal epithelial cells, and inhibited the inflammatory response. Bioinformatics was then used to construct the pharmacological network of SGD to explore its potential targets. SGD inhibited inflammatory response in mice with CAG by suppressing the expression of MAOB. Overexpression of MAOB impaired the therapeutic effect of SGD on inflammation in mice with CAG. Collectively, our findings indicated that SGD has the potential to alleviate CAG via downregulating MAOB.

Glioblastoma (GBM) is a malignant primary brain tumor and an essential contributor to morbidity and mortality globally. Arsenic trioxide (ATO) exerts specific roles in preventing tumor growth. This study investigated the role of ATO in GBM cell behaviors and stemness. The effects of ATO on the malignant behavior of GBM cells, tumor stemness, and epithelial-mesenchymal transition (EMT) factors in mouse tumor tissues were explored. Targets of ATO in GBM were predicted using multiple databases. Subsequently, the expression of retinoic acid-related orphan receptor beta (RORB), WNT-1, β-Catenin, and c-Myc expression were examined in GBM cells before and after ATO treatment.ATO inhibited the malignant behavior of GBM cells in vitro and slowed down the GBM growth in vivo by inhibiting the stemness. The inhibitory effect of ATO on GBM was achieved by promoting RORB levels and strengthening the antagonism to β-Catenin to inhibit Wnt signaling, thus inhibiting tumor growth. Collectively, ATO induced RORB levels in GBM cells and strengthened the antagonistic effect on β-Catenin, thus inhibiting WNT signaling and tumor growth.

In this study, we report two cases of siblings diagnosed with primary ciliary dyskinesia (PCD) sharing an identical genotype yet exhibiting distinct phenotypes. A 13-year-old girl with acute pneumonia was admitted to our hospital. Chest and sinus radiography revealed situs inversus and bilateral maxillary sinusitis. Chest computed tomography revealed bronchiectasis. Her 6-year-old brother with acute bronchitis was admitted and was diagnosed with bronchial asthma due to recurrent wheezing. Unlike his sister, he did not have situs inversus. Both patients had a chronic wet cough and were diagnosed with bronchial asthma by their family doctor. The mean PCD rule (PICADAR) scores were 9 and 7, respectively. Genetic analysis confirmed the presence of the same homozygous mutation (c.546C > A,pTyr182Ter) in DNAI2. To date, there have been four reports of the same pathogenic variants but different PCD phenotypes. Pathological variants of DNAI2 cause the loss of the outer dynein arm, the absence of which results in a lack of primary ciliary movement involved in the left-right axis formation during the embryonic period. A lack of functional cilia results in randomized visceral asymmetry; hence, the same pathogenic variant may exhibit different phenotypes. PCD is often overlooked and is sometimes managed as bronchial asthma, as in these siblings. In our case, the PICADAR score was useful in predicting the clinical diagnosis of PCD.