Int J Med Sci
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In traditional Korean medicine, the 16-herb concoction Bojanggunbi-tang (BGT) is used to treat various gastrointestinal (GI) diseases. In this study, we investigated the regulatory mechanism underlying the influence of BGT on the interstitial cells of Cajal (ICCs), pacemaker cells in the GI tract. Within 12 h of culturing ICCs in the small intestines of mice, the pacemaker potential of ICCs was recorded through an electrophysiological method. ⋯ Nonselective cation channel inhibitors, such as thapsigargin and flufenamic acid, along with protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) inhibitors, also suppressed the BGT reaction. Guanylate cyclase and protein kinase G (PKG) antagonists inhibited BGT, but adenylate cyclase and protein kinase A antagonists had no effect. In conclusion, we demonstrated that BGT acts through CHRM3, 5HTR3, and 5HTR4 to regulate intracellular Ca2+ concentrations and the PKC, MAPK, guanylate cycle, and PKG signaling pathways.
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Background: Interleukin-6 (IL-6)/soluble IL-6 receptor (sIL-6R) promotes peritoneal angiogenesis by stimulating SP4-mediated vascular endothelial growth factor (VEGF) production in peritoneal dialysis (PD). Moreover, histone methyltransferase enhancer of zeste homologue 2 (EZH2) is involved in IL-6/sIL-6R signalling via the acceleration of vascular endothelial growth factor (VEGF)-induced angiogenesis. However, the molecular mechanism underlying how EZH2 epigenetically activates VFGF expression in IL-6/sIL-6R signalling during PD is still unclear. ⋯ Moreover, IL-6/sIL-6R and EZH2 overexpression stimulated EZH2, DNMT3B and SP4 expression and promoted angiogenesis in 5/6Nx + PD rats. Conclusions: Thus, this study indicated that EZH2 is involved in IL-6/sIL-6R signalling and epigenetically regulates SP4 expression, thereby stimulating VEGF production and angiogenesis in PD. Targeting EZH2 is expected to be a novel therapeutic approach for end-stage renal disease (ESRD) patients with PD treatment.
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Background: Sideroflexins (SFXNs) are a family of highly conserved mitochondrial transporters which regulate iron homeostasis and mitochondrial respiratory chain. However, the roles and mechanisms of SFXNs in HCC remain unknown. Methods: SFXNs expression and prognostic value in HCC was comprehensively analyzed. ⋯ In vivo, knockdown of SFXN4 inhibited the growth of tumor xenografts in mice. Conclusion: SFXN4 was upregulated in HCC, predicted poor prognosis, and may facilitate HCC development and progression via various mechanisms. For HCC, SFXN4 may provide both prognostic information and therapeutic potential.
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Long non-coding RNAs are thought to play a vital role in a variety of human malignancies. Studies have shown that MIR155 host gene (MIR155HG) acts as an oncogene in several cancers, but the function and its mechanism of MIR155HG in gastric cancer (GC) is still poorly understood. In this study, we determined the biological functions and underlying mechanisms of MIR155HG in GC cells. ⋯ Moreover, cytotoxicity and apoptosis assays revealed overexpression of MIR155HG reduced the apotosis of GC cells induced by cisplatin and 5-FU. Together, our studies suggested that MIR155HG overexpression promoted proliferation, migration, and chemoresistance of GC cells. These results might provide a lncRNA-based target for GC treatment in future.
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Background: Treating renal fibrosis is crucial to delaying chronic kidney disease. The glycogen synthase kinase-3β (GSK-3β)/Snail pathway regulates renal fibrosis and Renalase can ameliorate renal interstitial fibrosis. However, it is not clear whether GSK-3β/Snail signaling affects Renalase action. ⋯ Furthermore, when an adeno-associated virus or plasmid was used to overexpress GSK-3β, the effect of Renalase on delaying renal fibrosis was counteracted, although ER stress markers did not change. Conclusion: Renalase prevents renal fibrosis by down-regulating GSK-3β/Snail signaling through inhibition of ER stress. Exogenous Renalase may be an effective method of slowing or stopping chronic kidney disease progression.