Glycycoumarin (GCM) is a representative of bioactive coumarin compounds isolated from licorice, an edible and medicinal plant widely used for treating various diseases including liver diseases. The purpose of the present study is to examine the possibility of GCM as a sensitizer to improve the efficacy of BH3 mimetic ABT-737 against liver cancer. Three liver cancer cell lines (HepG2, Huh-7 and SMMC-7721) were used to evaluate the in vitro combinatory effect of ABT-737/GCM. HepG2 xenograft model was employed to assess the in vivo efficacy of ABT-737/GCM combination. Results showed that GCM was able to significantly sensitize liver cancer cells to ABT-737 in both in vitro and in vivo models. The enhanced efficacy by the combination of ABT-737 and GCM was attributed to the inactivation of T-LAK cell-originated protein kinase (TOPK)-survivin axis and inhibition of de novo lipogenesis. Our findings have identified induction of TOPK-survivin axis as a novel mechanism rendering cancer cells resistant to ABT-737. In addition, ABT-737-induced platelet toxicity was attenuated by the combination. The findings of the present study implicate that bioactive coumarin compound GCM holds great potential to be used as a novel chemo-enhancer to improve the efficacy of BH3 mimetic-based therapy.

Circular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs with a closed-loop structures, and they exert crucial regulatory functions in diverse biological processes and disease development through the modulation of linear RNA transcription, downstream gene expression, and protein translation, among others. Circular RNA FOXO3(circFOXO3, Hsa_circ_0006404) originates from exon 2 of the FOXO3 gene and exhibits widespread cytoplasmic expression in eukaryotic cells. It shows specific expression in different tissues or cells. Recent research has associated circFOXO3 with various diseases such as cancer, cardiovascular diseases, neurological disorders, senescence, and inflammation. However, a comprehensive review of the research progress of circFOXO3 in human diseases has not been conducted. In this paper, we provide a systematic review of the latest advances in circFOXO3 research in diseases, elucidate its biological functions and potential molecular mechanisms, and discuss the future directions and challenges in circRNAs research to provide valuable references and inspiration for research in this field.

Pediatric sepsis syndrome is one of the most common reasons for pediatric intensive care unit hospitalization (PICU). Cefoperazone/sulbactam is a time-dependent beta-lactamase inhibitor combination which has been widely used in the treatment of sepsis. But the pharmacokinetic (PK) and pharmacodynamic (PD) data of cefoperazone/sulbactam are unknown in children with sepsis. The present work aimed to determine whether the usual dosing regimens of cefoperazone/sulbactam (1 hour infusion, 50 mg kg⁻¹, every 12 hours) were suitable for these patients in PICU. A total of fourteen patients were enrolled and the PK parameters were estimated by non-compartmental analysis using WinNonlin software. The t_1/2 and AUC_0–12 of cefoperazone and sulbactam were 3.60 and 1.77 h, and 900.97 and 67.68 h μg mL⁻¹, respectively. The Vd and CL of cefoperazone and sulbactam were 1.65 L and 5.16 L, and 17.41 mL min⁻¹ and 122.62 mL min⁻¹, respectively. The probability of target attainments (PTAs) of cefoperazone at different minimum inhibitory concentrations (MICs) based on the percentage time that concentrations exceed the minimum inhibitory concentration (% T > MIC) value were performed by Monte Carlo simulation and PTA was >90% at MICs ≤16 μg mL⁻¹. The PK/PD profile of dosing regimens tested will assist in selecting the appropriate cefoperazone/sulbactam regimens for these patients. At a target of 80% T > MIC, the usual dosing regimens can provide good coverage for pathogens with MICs of ≤32 μg mL⁻¹. The ratio between cefoperazone and sulbactam at 1 : 1 may be more suitable in pediatric sepsis. Individual dose and therapeutic drug monitoring in clinical practice will help achieve the best therapeutic effect while minimizing toxicity.