Int J Med Sci
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Autosomal dominant tubulointerstitial kidney disease due to UMOD mutations (ADTKD-UMOD) results in chronic interstitial nephritis, which gradually develops into end-stage renal disease. It is believed that the accumulation of mutant uromodulin causes the endoplasmic reticulum (ER) stress, then leads to the kidney damage. But the underlying mechanism remains unclear. ⋯ Moreover in vitro experiments, ER stress induced by tunicamycin (TM) not only significantly increased the expression of GRP78 and CHOP, but also caused the epithelial to myofibroblast transformation (EMT) of renal tubular epithelial cells, evidenced by decreased expression of E-cadherin and increased expression of vimentin, and extracellular matrix (ECM) deposition, evidenced by increased expression of fibronectin (FN). CHOP knockdown could restore the upregulation of vimentin and FN induced by TM. Thus, specific activation of CHOP in renal tubular epithelial cells induced by UMOD protein might be the key reason of renal interstitial fibrosis in ADTKD-UMOD patients.
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Preeclampsia is one of the most serious pregnancy complications. It may be caused by immunological changes in the early placental microenvironment. The contents of small EVs may serve as biomarkers of pregnancy complications. ⋯ The ROC analysis showed that the classification efficiency (AUC) of TGF-β in small EVs was 0.81. TGF-β had the best discriminant ability of all the single EV biomarkers tested, the cross-validation of the accuracy was 0.89. Th17 and Treg cytokines in plasma and small EVs may contribute to maternal immune activation and clarify the potential mechanisms of small EVs and cytokines in preeclampsia.
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Uterine corpus endometrial carcinoma (UCEC) is one of the most common types of cancer in women, and the incidence is rapidly increasing. Studies have shown that various signaling pathways serve crucial roles in the tumorigenesis of UCEC, amongst which the Wnt/β-catenin pathway is of great interest due to its crucial role in cell proliferation and the huge potential as a therapeutic target. ⋯ Besides, the results suggested that FBXO17 may inhibit the Wnt/β-catenin signaling pathway and influence the expression of adhesion molecules, such as E-cadherin and N-cadherin in Ishikawa cells. In conclusion, these findings indicate that FBXO17 is a novel inhibitor of endometrial tumor development and it likely exerts effects via regulation of the Wnt signaling pathway.
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Background: The previous studies have revealed that IL-27 was involved in the pathophysiology of pulmonary inflammatory diseases. However, the role of IL-27 in community-acquired pneumonia (CAP) was unclear. The goal of this research was to explore the associations of serum IL-27 with the severity and prognosis among CAP patients through a prospective cohort study. ⋯ Logistic regression analysis demonstrated that serum higher IL-27 on admission elevated the risks of vasoactive agent usage and longer hospital stay during hospitalization among CAP patients. Conclusions: Serum IL-27 is markedly and positively associated with the severity and poor prognosis among CAP patients, indicating that IL-27 may involve in the pathophysiological process of CAP. Serum IL-27 may be used as a biomarker for diagnosis and prognosis in CAP patients.
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Sorafenib resistance is a major challenge in the treatment of patients with advanced hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) are a large family of non-coding RNA molecules, which is an important mechanism of drug resistance. We previously found that knockdown of miR-25 increased the sensitivity of TRAIL-induced apoptosis in liver cancer stem cells. ⋯ Our results suggested that miR-25 increased the sorafenib resistance of HCC via inducing autophagy. In addition, miR-25 decreases the expression of FBXW7 protein to regulate autophagy. Therefore, miR-25 may represent a novel therapeutic target for the treatment of HCC.