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 and aims: Macrophages play a critical role in the development of liver diseases. As an NAD+-dependent histone deacetylase, SIRT1 inhibits liver inflammation and fibrosis, but the mechanisms are not fully understood. Our aim was to investigate the molecular mechanism of SIRT1 in macrophages in liver inflammation and fibrosis. ⋯ Nevertheless, knockdown of NF-κB or NLRP3 and activation of SIRT1 inhibited inflammation of macrophages; inhibition or knockdown of SIRT1 enhanced macrophage inflammation. Furthermore, activation of SIRT1 could inhibit LPS-treated macrophages from activating hepatic stellate cells (HSCs). Conclusions: Activating SIRT1 inhibits the inflammation in macrophages by down-regulating NLRP3 pathway through deacetylating NF-κB p65, which in turn inhibits the activation of HSCs to alleviate hepatic inflammation and fibrosis.
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Cancer has been linked to metabolic disorders and diverse gene mutations. Metformin, which is widely used to treat type 2 diabetes, inhibits the growth of cancer cells in animal models. Here we investigated the effects of metformin on human gastric cancer cell lines. ⋯ Our results revealed that metformin and lansoprazole can significantly inhibit cancer cell growth in a dose-dependent manner by suppressing cell cycle progression and inducing apoptosis. Low concentrations of metformin and lansoprazole have a synergistic effect on AGS cell growth inhibition. In summary, our findings suggest a new and safe treatment protocol for treating stomach cancers.
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The development of endocrine therapy resistance in the luminal A subtype of breast cancer is related to the appearance of protective autophagy. The bioactive component from the root of licorice, 18β-glycyrrhetinic acid (18β-GA), has many antitumor properties. Whether 18β-GA can modulate autophagy to inhibit proliferation of the luminal A subtype is still unclear. ⋯ A JNK inhibitor (SP600125) significantly inhibited 18β-GA-mediated apoptosis, LC3-II accumulation and rescued the numbers of MCF-7 and T-47D colony formation. Especially, 18β-GA can inhibit xenograft tumor growth in BALB/c nude mice. These data indicate the combination of 18β-GA with rapamycin or 3-MA can sensitize or decrease MCF-7 and T-47D cells to 18β-GA-induced apoptosis, respectively. 18β-GA modulated autophagy is cytotoxic to luminal A subtype breast cancer cells through apoptosis promotion and JNK activation.
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Introduction: Hepatic ischemia/reperfusion (I/R) injury is common after liver surgery, particularly in patients of older age. However, an understanding of the mechanism of injury remains incomplete. In this study, we explored the molecular mechanisms underlying hepatic I/R injury and associations with age in a murine model. ⋯ Before and after hepatic I/R injury, mmu-miR-9-5p, mmu-miR-329-3p, and mmu-miR-290a-5p showed significant differential expression both in young (1 month old) and old (1 year old) mice. miR-329-3p had the most significant differential expression, and its predicted target genes Adamts4 and Dnajb1 were also significantly upregulated. Conclusions: The decrease in miR-329-3p expression upregulated Adamts4 and Dnajb1 expression in mouse hepatic I/R injury in an age-independent manner. This finding contributes to our understanding of hepatic I/R injury, and highlights novel molecular targets for future therapeutic development.