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Background and aimsVonoprazan, a novel acid suppressant, has been employed in the treatment of peptic ulcer disease in recent years. However, the efficacy and safety of vonoprazan versus proton-pump inhibitors remains controversial. To address this gap, a systematic review and network meta-analysis were conducted to evaluate the efficacy and safety of vonoprazan in comparison with various proton-pump inhibitors.MethodsRandomized controlled trials that met selection criteria in PubMed (Medline), EMBASE and the Cochrane Library were searched up to July 15, 2024. The primary outcome was ulcer healing rate. Secondary outcomes were treatment-emergent adverse events and drug-related adverse events. Effect size on outcomes is presented as odds ratios with 95% confidence intervals.ResultsThirty-five randomized controlled trials containing 9,544 participants were included. In terms of the healing rate at 2 weeks, lansoprazole 30 mg ranked first, followed by vonoprazan 20 mg and ilaprazole 10 mg. In terms of the healing rate at 4 weeks, pantoprazole 40 mg ranked first, with rabeprazole 10 mg and lansoprazole 30 mg ranking second and third, respectively. Regarding the healing rate at 8 weeks, lansoprazole 30 mg is demonstrated to be the most efficacious regimen. Moreover, subgroup analysis indicated that lansoprazole 30 mg is the optimal regimen in the treatment of artificial gastric ulcer at 4 and 8 weeks. Importantly, lansoprazole 30 mg has fewer adverse reactions and higher safety.ConclusionThe optimal regimen for the treatment of peptic ulcer disease may be lansoprazole 30 mg at 2 and 8 weeks, while pantoprazole 40 mg has demonstrated superior performance at the 4-week when compared to vonoprazan 20 mg. Furthermore, lansoprazole 30 mg has shown to be superior in terms of safety outcomes. These findings, derived from a network meta-analysis, necessitate further research for validation.

AbstractBackground/Aims Colorectal cancer is the third leading cause of death in patients with cancers in America. Monensin has represented anti-cancer effect on various human cancer cells. We seek to investigate the effect of monensin on proliferation of human colorectal cancer cells and explore whether IGF1R signaling pathway is involved in anti-cancer mechanism of monensin.Methods Cell proliferation and migration were assessed by crystal violet staining and cell wounding assay respectively. Cell apoptosis was analyzed by Hoechst 33258 staining and flow cytometry. Cell cycle progression was detected with the use of flow cytometry. Cancer-associated pathways were assessed with the use of pathway-specific reporters. Gene expression was detected by touchdown-quantitative real-time PCR. Inhibition of IGF1R was tested by immunofluorescence staining. Inhibition of IGF1R signaling was accomplished by adenovirus-mediated expression of IGF1.Results We found that monensin not only effectively inhibited cell proliferation, cell migration as well as cell cycle progression, but also induced apoptosis and G1 arrest in human colorectal cancer cells. Monensin was shown to target multiple cancer-related signaling pathways such as Elk1, AP1, as well as Myc/max, and suppressed IGF1R expression via increasing IGF1 in colorectal cancer cells.Conclusion Monensin could suppressed IGF1R expression via increasing IGF1 in colorectal cancer cells. It has the potential to be repurposed as an anti-colorectal cancer agent, but further studies are still required to investigate the detailed mechanisms of monensin underlying its anti-cancer motion.Key MessagesMonensin inhibits the cell proliferation and the migration, induces apoptosis and inhibits cell cycle progression in human colorectal cancer cells.Monensin may exert anti-cancer activity by targeting multiple signaling pathways, including the IGF1R signaling pathway.Monensin has the potential to be repurposed as an anti-colorectal cancer agent.

Abstract Background The aim of this study was to investigate how the signaling pathway downstream of mTOR/S6K1 contributes to the regulation of SREBP-1c expression during lipogenesis in HepG2 cells. Methods The model of steatosis was established using human hepatocytes HepG2 and inducting them with sodium palmitate. mTOR, S6K1 and LXRα were inhibited by rapamycin, PF-4708671 and siRNA-LXRα, respectively. After a variety of different treatment, the levels of intracellular triglycerides, the accumulation of lipid droplets and the expression levels of related genes were detected. Results Rapamycin, PF-4708671 and siRNA-LXRα treatment could decrease the accumulation of triglycerides and lipid droplets induced by sodium palmitate in HepG2 cells, and the inhibitory effect could be enhanced by the combination of them. Sodium palmitate stimulated the expression of genes encoding mTOR, S6K1, LXRα, SREBP-1c and SREBP-1c target enzymes (FAS and ACC1) in HepG2 cells. Moreover, these genes were sensitive to rapamycin. PF-4708671 also decreased the expression of these genes, except for the mTOR gene, and the extent of reduction could be enhanced by combination with rapamycin. Knockdown of LXRα decreased the expression of SREBP-1c, FAS and ACC1, but it had no effect on the expression of mTOR or S6K1. Furthermore, rapamycin and PF-4708671 enhanced the inhibitory effect of siRNA-LXRα. Conclusions mTOR/S6K1 regulates the SREBP-1c signaling pathway through LXRα in sodium palmitate-induced HepG2 cells, suggesting LXRα might be a potential therapeutic target for NAFLD.

Lipidomic approaches are now widely used to investigate the relationship between lipid metabolism, health and disease. Large-scale lipidomics studies typically aim to quantify hundreds to thousands of lipid molecular species in a large number of samples. Consequently, high throughput methodology that can efficiently extract a wide range of lipids from biological samples is required. Current methods often rely on extraction in chloroform:methanol with or without two phase partitioning or other solvents, which are often incompatible with liquid chromatography electrospray ionization-tandem mass spectrometry (LC ESI-MS/MS). Here, we present a fast, simple extraction method that is suitable for high throughput LC ESI-MS/MS. Plasma (10 μL) was mixed with 100 μL 1-butanol:methanol (1:1 v/v) containing internal standards resulting in efficient extraction of all major lipid classes (including sterols, glycerolipids, glycerophospholipids and sphingolipids). Lipids were quantified using positive-ion mode LC ESI-MS/MS. The method showed high recovery (>90%) and reproducibility (%CV < 20%). It showed a strong correlation of all lipid measures with an established chloroform:methanol extraction method (R2 = 0.976). This method uses non-halogenated solvents, requires no drying or reconstitution steps and is suitable for large-scale LC ESI-MS/MS-based lipidomic analyses in research and clinical laboratories.