Dietary protein or amino acid (AA) is a crucial nutritional factor to regulate hepatic insulin-like growth factor-1 (IGF-1) expression and secretion. However, the underlying intracellular mechanism by which dietary protein or AA induces IGF-1 expression remains unknown. We compared the IGF-1 gene expression and plasma IGF-1 level of pigs fed with normal crude protein (CP, 20%) and low-protein levels (LP, 14%). RNA sequencing (RNA-seq) was performed to detect transcript expression in the liver in response to dietary protein. The results showed that serum concentrations and mRNA levels of IGF-1 in the liver were higher in the CP group than in the LP group. RNA-seq analysis identified a total of 1319 differentially expressed transcripts (667 upregulated and 652 downregulated), among which the terms “oxidative phosphorylation”, “ribosome”, “gap junction”, “PPAR signaling pathway”, and “focal adhesion” were enriched. In addition, the porcine primary hepatocyte and HepG2 cell models also demonstrated that the mRNA and protein levels of IGF-1 and PPARγ increased with the increasing AA concentration in the culture. The PPARγ activator troglitazone increased IGF-1 gene expression and secretion in a dose dependent manner. Furthermore, inhibition of PPARγ effectively reversed the effects of the high AA concentration on the mRNA expression of IGF-1 and IGFBP-1 in HepG2 cells. Moreover, the protein levels of IGF-1 and PPARγ, as well as the phosphorylation of mTOR, significantly increased in HepG2 cells under high AA concentrations. mTOR phosphorylation can be decreased by the mTOR antagonist, rapamycin. The immunoprecipitation results also showed that high AA concentrations significantly increased the interaction of mTOR and PPARγ. In summary, PPARγ plays an important role in the regulation of IGF-1 secretion and gene expression in response to dietary protein.

No abstract

Ulcerative colitis (UC), one of the foremost common forms of inflammatory bowel disease, poses a serious threat to human health. Currently, safe and effective treatments are not available. This study investigated the protective effect of ginkgolide C (GC), a terpene lactone extracted from Ginkgo biloba leaves, on UC and its underlying mechanism. The results showed that GC remarkably mitigated the severity of DSS-induced colitis in mice, as demonstrated by decreased body weight loss, reduced disease activity index, mitigated tissue damage, and increased colon length. Furthermore, GC inhibited DSS-induced hyperactivation of inflammation-related signaling pathways (NF-κB and MAPK) to reduce the production of inflammatory mediators, thereby mitigating the inflammatory response in mice. GC administration also restored gut barrier function by elevating the number of goblet cells and boosting the levels of tight junction-related proteins (claudin-3, occludin, and ZO-1). In addition, GC rebalanced the intestinal flora of DSS-treated mice by increasing the diversity of the flora, elevating the abundance of beneficial bacteria, such as Lactobacillus and Allobaculum, and decreasing the abundance of harmful bacteria, such as Bacteroides, Oscillospira, Ruminococcus, and Turicibacter. Taken together, these results suggest that GC administration effectively alleviates DSS-induced colitis by inhibiting the inflammatory response, maintaining mucosal barrier integrity, and regulating intestinal flora. This study may provide a scientific basis for the rational use of GC in preventing colitis and other related diseases.

No abstract

Previous studies have demonstrated that microRNAs (miRs) serve important roles in the progression of human cancer types, including pancreatic cancer (PC), a highly lethal malignancy. In the past few decades, several miRs have been identified to be associated with the overall survival of patients with PC and have been demonstrated to be potential therapeutic targets. However, to the best of our knowledge, the association between miR-205 expression and the progression of PC has rarely been investigated. In the current study, low miR-205 expression was revealed in PC tumor tissues and indicated poor prognosis in patients with PC. In addition, miR-205 overexpression reduced and miR-205 depletion enhanced PC cell proliferation and migration in vitro. Using bioinformatics, a luciferase reporter assay and western blot analyses, the current study identified that runt-related transcription factor 2 (RUNX2) was a target of miR-205 in PC and overexpression of miR-205 suppressed the expression of RUNX2. Notably, overexpression of RUNX2 partially reversed the inhibitory effect of miR-205 on PC cell proliferation and migration in vitro. Therefore, the results of the present study revealed that miR-205 functions as a tumor suppressor in PC by targeting RUNX2.