Rhizoma Paridis Saponins (RPS), a natural compound purified from Rhizoma Paridis, has been found to inhibit cancer growth in vitro and in animal models of cancer. However, its effects on esophageal cancer remain unexplored. The purpose of this study was to investigate the effects of RPS on tumor growth in a rat model of esophageal cancer and the molecular mechanism underlying the effects. A rat model of esophageal cancer was established by subcutaneous injection of N-nitrosomethylbenzylamine (NMBA, 1mg/kg) for 10 weeks. RPS (350 mg/kg or 100mg/kg) was administered by oral gavage once daily for 24 weeks starting at the first NMBA injection. RPS significantly reduced the size and number of tumors in the esophagus of rats exposed to NMBA and inhibited the viability, migration, and invasion of esophageal cancer cells EC9706 and KYSE150 in a dose dependent manner (all P < 0.01). Flow cytometry revealed that RPS induced apoptosis and cell cycle G2/M arrest in the esophageal cancer cells. The expression of cyclooxygenases-2 (COX-2) and Cyclin D1 in rat esophageal tissues and the esophageal cancer cells were also significantly reduced by RPS (all P < 0.01). Consistently, RPS also significantly decreased the release of prostaglandin E2, a downstream molecule of COX-2, in a dose-dependent manner (P < 0.01). Our study suggests that RPS inhibit esophageal cancer development by promoting apoptosis and cell cycle arrest and inhibiting the COX-2 pathway. RPS might be a promising therapeutic agent for esophageal cancer.
Aims. Fibroblast growth factor receptor 4 (FGFR4) is a key mediator that protects the liver from chronic injury. MicroRNA-7 (miR-7) is a tumor suppressor and associated with lipid homeostasis in the liver. This study was designed to examine the role of the miR-7-5p/FGFR4 axis in liver fibrogenesis. Methods. TargetScan was employed to predict microRNAs that targeted FGFR4 on the 3′-untranslated region (3′-UTR). miR-7-5p and FGFR4 expression in pathological liver tissues and LX-2 cells was determined using qRT-PCR and an immunoblotting assay. A dual-luciferase assay was conducted to validate the target prediction. A Cell Counting Lit-8 assay was performed to assess the proliferation ability of LX-2 cells. Hydroxyproline content in LX-2 cells was measured using a hydroxyproline assay. The expression of hepatic stellate cell (HSC) activation markers was examined using qRT-PCR and an immunoblotting assay. Results. FGFR4 was a putative target of miR-7-5p. In LX-2 cells, miR-7-5p targeted FGFR4 by binding to 3′-UTR. FGFR4 was downregulated, but miR-7-5p was markedly enhanced in the liver samples as the degree of liver fibrosis rose. miR-7-5p was negatively associated with FGFR4 expression in liver tissues. The miR-7-5p inhibitor blocked the lipopolysaccharide-induced proliferation and activation of LX-2 cells, and FGFR4 overexpression inhibited LX-2 cell proliferation and activation triggered by miR-7-5p. Conclusion. miR-7-5p promotes HSC proliferation and activation by downregulating FGFR4.
Aims: Intravenous ibuprofen (IVIB) has been approved in the treatment of
postoperative pain and fever in adults, but the application of multiple-
or single- dosage IVIB remains divergent in clinical practice. This
study aims to evaluate the efficacy and safety of IVIB in the management
of postoperative pain and fever in adults who were unable to take oral
medicine. Methods: A systematic review and meta-analysis was conducted
based on randomized controlled trials (RCTs) regarding postoperative
pain and fever management comparing IVIB with placebo, or other
analgesic and antipyretic agents from 8 databases. Risk of bias and
quality of evidence assessment were performed. The primary outcomes
mainly included visual analogue scale (VAS) score within postoperative
24h and the reduction of temperature. Results: Twenty-three RCTs with
3716 participants were included. For postoperative pain, moderate-to-low
certainty evidence indicated that IVIB was associated with lower
postoperative VAS scores than placebo, with MD ranging between -3.53
(95% CI, -4.32 to -2.75) at 0 minute to -0.96 (95% CI, -1.35 to -0.57)
at 24 hours. Compared to intravenous acetaminophen, IVIB appeared lower
VAS scores (MD, -1.54 at 0min; -0.36 at 24h). For fever, IVIB appeared
satisfactory antipyretic efficiency in a short period of time, but there
was no difference between IVIB and intravenous acetaminophen.
Moderate-to-low certainty evidence indicated that IVIB was well
tolerated in both pain and fever management. Conclusions:
Moderate-to-low certainty evidence supported that adults with
postoperative pain and fever who were unable to take oral medicine would
benefit from IVIB.
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