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Background: The manipulation of ferroptosis in cancer cells is a possible therapeutic technique that has been investigated for use in the treatment of cancer. Consequently, ferroptosis-inducing medications have recently received increased interest in cancer therapy. In this research, we assessed the anticancer efficacy of 14β-hydroxy- 3β-(β-D-Glucopyranosyloxy)-5α-bufa-20,22-dienolide (HTB50-2), a natural product derived from the plant Helleborus thibetanus Franch, in Triple-Negative Breast Cancer (TNBC). Moreover, we also studied its potential mechanisms., Methods: The biological effects of HTB50-2 in a series of breast cancer cell lines were analyzed using sulforhodamine B (SRB) and other methods. The migration ability was analyzed using three methods: wound healing assay, transwell assay, and Western blot. Meanwhile, the potential therapeutic value of HTB50-2 was evaluated in BALB/c mice by orthotopic transplantation. Transcriptome sequencing was conducted to explore the FOS-like antigen 2 (FOSL2) gene, and its role in ferroptosis was verified by Western blot and immunohistochemistry. The association of FOSL2 and ferroptosis-related genes was analyzed using NetworkAnalyst databases, and a TF-Gene interaction network was constructed., Results: Ferroptosis was found to be induced in TNBC cells by HTB50-2. Furthermore, HTB50-2 inhibited tumor development by inducing ferroptosis in TNBC in vivo. Mechanistically, we demonstrated that a transcription factor FOSL2 mediated ferroptosis by HTB50-2. Additionally, it was found that Forkhead box C1 (FOXC1) was regulated by FOSL2 and correlated with ferroptosis., Conclusion: Our data suggest that HTB50-2 exerts its anti-cancer properties by ferroptosis via FOSL2/FOXC1 signaling pathway. Hence, HTB50-2 has an important application potential in the treatment of TNBC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Postoperative ileus (POI) is a common obstruction of intestinal content passage caused by almost all abdominal operations that seriously strokes the quality of life of patients. Kuanchang-Shu granule (KCSG), a classic modified prescription based on "Da-Cheng-Qi Decoction", has obtained satisfactory efficacy in the clinical therapeutics of POI. However, its material basis and holistic molecular mechanism against POI have not been revealed., Methods: The chemical ingredients of KCSG were first characterized by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Subsequently, an integration strategy of the network pharmacology and molecular docking based on above identified ingredients was performed to unveil the potential targets involved in the treatment of KCSG on POI. Finally, intestinal manipulation induced rat POI model was constructed to verify the efficacy and predicted mechanism of KCSG against POI., Results: In total, 246 ingredients mainly including organic acids, flavonoids, quinones, alkaloids, terpenoids, phenylpropanoids and phenols were identified. 41 essential ingredients, 24 crucial targets as well as 15 relevant signaling pathways were acquired based on network pharmacology analysis. Pharmacodynamic research showed that KCSG treatment could protect intestinal histological damage, promote the recovery of measurement of gastrointestinal transit disorder and inhibit the secretion of myeloperoxidase in the distal ileum tissues. The up-regulated expression of p-AKT and down-regulated expression of p-eNOS and HSP9OAA1 predicted by molecular docking and validated by western blotting showed that AKT/eNOS/HSP90AA1 pathway may be one of the crucial mechanisms that mediates the protective effect of KCSG., (© 2024. The Author(s).)

Background: Compounds that target tumor epigenetic events are likely to constitute a prominent strategy for anticancer treatment. Histone deacetylase inhibitors (HDACis) have been developed as prospective candidates in anticancer drug development, and currently, many of them are under clinical investigation. We assessed the anticancer efficacy of a now hydroxamate-based HDACi, YF-343, in triple-negative breast cancer development and studied its potential mechanisms., Methods: YF-343 was estimated as a novel HDACi by the HDACi drug screening kit. The biological effects of YF-343 in a panel of breast cancer cell lines were analyzed by Western blot and flow cytometry. YF-343 exhibited notable cytotoxicity, promoted apoptosis, and induced cell cycle arrest. Furthermore, it also induced autophagy, which plays a pro-survival role in breast cancer cells., Results: The combination of YF-343 with an autophagy inhibitor chloroquine (CQ) significantly suppressed breast tumor progression as compared to the YF-343 treatment alone both in vitro and in vivo . Mechanistically, the molecular mechanism of YF-343 on autophagy was elucidated by gene chip expression profiles, qPCR analysis, luciferase reporter gene assay, chromatin immunoprecipitation assays, immunohistochemical analysis, and other methods. E2F7, a transcription factor, promoted the expression of ATG2A via binding to the ATG2A promoter region and then induced autophagy in triple-negative breast cancer cells treated with YF-343., Conclusion: Our studies have illustrated the mechanisms for potential action of YF-343 on tumor growth in breast cancer models with pro-survival autophagy. The combination therapy of YF-343 and CQ maybe a promising strategy for breast cancer therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To assess the effect of a novel naturally cultured rice with high resistant starch (RS) on postprandial glycemia in patients with type 2 diabetes compared to ordinary rice., Design: This study is a randomized, double-blinded controlled trial., Methods: Patients with type 2 diabetes were recruited, and postprandial glucose levels were measured at 5-time points after the ingestion of one of two types of cooked rice in random order. Paired t -tests were used to compare postprandial blood glucose changes and increment areas under the blood glucose curve between high-RS rice and ordinary rice., Results: The increments of the postprandial blood glucose levels for high-RS rice were significantly lower than that for ordinary rice, i.e., 2.80 ± 1.38 mmol/L vs. 3.04 ± 1.50 mmol/L ( P = 0.043) and 3.94 ± 2.25 mmol/L vs. 4.25 ± 2.29 mmol/L ( P = 0.036) at 30 min and 60 min, respectively. The incremental areas under the blood glucose curve for high-RS rice were also significantly lower than that for ordinary rice, i.e., 42.04 ± 20.65 [mmol/(L·min)] vs. 45.53 ± 22.45 [mmol/(L·min)] ( P = 0.043), 143.54 ±69.63 [mmol/(L·min)] vs. 155.15 ± 73.53 [mmol/(L·min)] ( P = 0.026), and 354.61 ± 191.96 [mmol/(L·min)] vs. 379.78 ± 195.30 [mmol/(L·min)] ( P = 0.042) at 30, 60, and 120 min, respectively. Repeated-measures ANOVA showed that postprandial glucose levels were not affected by the test order., Conclusion: The novel high-RS rice as a staple food when substituting for widely consumed ordinary rice may provide potential health benefits by lowering blood glucose in patients with type 2 diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tan, Duan, Chen, Mei, Qi and Zhang.)