Int J Med Sci
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The highly conserved Hippo signaling pathway is one of the most important pathways involved in tumorigenesis and progress. Previous studies show that YAP, the transcriptional coactivator of Hippo pathway, is expressed highly in many clinical bladder cancer tissues and plays crucial role on bladder cancer progress. To find the YAP-specific target drug and its molecular mechanism in bladder cancer, we apply Verteporfin (VP), a YAP specific inhibitor to function as anti-bladder cancer drug and discover that VP is able to inhibit bladder cancer cell growth and invasion in a dosage dependent manner. ⋯ In further study, we provide evidence that VP is able to inhibit excessive YAP induced bladder cancer cell growth and invasion. To address the repressive function of VP against YAP in bladder cancer, we check the target genes' expression and find VP can dramatically repress YAP overexpression induced Hippo pathway target genes' expression. Taken together, we discover that VP inhibits YAP-induced bladder cancer cell growth and invasion via repressing the target genes' expression of Hippo signaling pathway.
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In the last 10 years the number of studies showing the benefits of resistance training (RT) to the cardiovascular system, have grown. In comparison to aerobic training, RT-induced favorable adaptations to the cardiovascular system have been ignored for many years, thus the mechanisms of the RT-induced cardiovascular adaptations are still uncovered. The lack of animal models with comparable protocols to the RT performed by humans hampers the knowledge. ⋯ However, to a lesser extent, other models are also employed to investigate the cardiovascular adaptations. In the subsequent sections we will review the information regarding cardiac morphological adaptations, signaling pathway of the cardiac cell, cardiac function and the vascular adaptation induced by RT using this animal model developed by Tamaki et al. in 1992. Furthermore, we also describe cardiovascular findings observed using other animal models of RT.
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Background: Keratinocytes are the predominant cell type in a cholesteatoma, and microRNA (miR)-203a has been shown to be essential for the growth and differentiation of keratinocytes. The regulatory mechanisms of miR-203a and Bmi1-the predicted target of miR-203a that is associated with cholesteatoma-have not been clarified. Methods: Real-time PCR and western blot were carried out for the detection of miRNAs, mRNAs, and proteins, including miR-203a, Bmi1, and phosphorylated (p-)Akt. ⋯ Suppression of Bmi1 reduced p-Akt expression in HaCaT cells; subsequent inhibition of miR-203a reversed this phenomenon. Conclusions: Our results reveal that miR-203a may regulate cholesteatoma growth and proliferation by targeting Bmi1. These findings provide insight for the development of novel nonsurgical options for cholesteatoma.
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Background: Psoriasis is one of the most common chronic, life-long dermatologic diseases, which has considerable negative effects on quality of life. Psoriasis is considered as a systemic inflammatory disease, thus acute phase proteins such as C-reactive protein (CRP) and orosomucoid (ORM) have been shown to play a role in its pathophysiology. This study was aimed to compare CRP, serum ORM (se-ORM) and urinary ORM (u-ORM) levels of psoriatic patients to healthy individuals. ⋯ No significant differences were found between the groups regarding se-ORM levels. HsCRP, se-ORM and u-ORM/u-CREAT levels were significantly higher in patients with severe psoriasis than in mild and moderate cases (p<0.05). Conclusion: As a highly sensitive, easily available biomarker u-ORM shows itself capable of becoming a new inflammatory marker in psoriasis providing clinically useful information on disease severity.
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Although miRNA markers have been identified for the pathological development of gastric adenocarcinoma (GAC), the underlying molecule mechanism are still not fully understood. Moreover, some gastric adenoma/dysplasia may progress to GAC. In this study, the miRNA expression profiles in normal and paired low-/high-grade dysplasia were analyzed using Affymetrix Gene-Chip miRNA arrays. ⋯ The analysis revealed that hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p were overexpressed in gastric low-/high-grade dysplasia and that based on these miRNA-target interactions, FBXO11 and CREBZF could be considered convincing markers for gastric cancer (GC) progression. Thus, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the GC development from premalignant adenomas. Furthermore, these two target mRNAs and three miRNAs were predicted to be potential biomarkers for the progression of GC by miRNA-target interaction analysis.