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Simple Summary: Further investigation into the molecular mechanisms of chemotherapy resistance in pancreatic cancer is crucial for improving the prognosis of pancreatic cancer patients. Extensive research has demonstrated a close association between ferroptosis and gemcitabine resistance in various tumor types, including pancreatic cancer. We first show that high expression of Mitotic checkpoint serine/threonine kinase BUB1 in pancreatic cancer and its association with poor prognosis. Results also suggested that BUB1 suppresses ferroptosis in pancreatic cancer cells, and BUB1 knockdown significantly enhances the sensitivity of drug-resistant pancreatic cancer cells to ferroptosis. Furthermore, BUB1 promotes gemcitabine resistance in pancreatic cancer cells. We believe that our study makes a significant contribution to the literature because it was previously unclear whether BUB1 plays a key role in pancreatic cancer ferroptosis. The development of chemotherapy resistance severely limits the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer (PC), and the dysregulation of ferroptosis is a crucial factor in the development of chemotherapy resistance. BUB1 Mitotic Checkpoint Serine/Threonine Kinase (BUB1) is highly overexpressed in PC patients and is closely associated with patient prognosis. However, none of the literature reports the connection between BUB1 and ferroptosis. The molecular mechanisms underlying GEM resistance are also not well understood. Therefore, this study first established the high expression levels of BUB1 in PC patients, then explored the role of BUB1 in the process of ferroptosis, and finally investigated the mechanisms by which BUB1 regulates ferroptosis and contributes to GEM resistance in PC cells. In this study, downregulation of BUB1 enhanced the sensitivity of PC cells to Erastin, and inhibited cell proliferation and migration. Mechanistically, BUB1 could inhibit the expression levels of Neurofibromin 2 (NF2) and MOB kinase activator 1 (MOB1), and promote Yes-associated protein (YAP) expression, thereby inhibiting ferroptosis and promoting GEM resistance in PC cells. Furthermore, the combination of BUB1 inhibition with GEM exhibited a synergistic therapeutic effect. These findings reveal the mechanisms underlying the development of GEM chemotherapy resistance based on ferroptosis and suggest that the combined use of BUB1 inhibitors may be an effective approach to enhance GEM efficacy. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a non-infectious pancreatic enzyme-induced disorder, a life-threatening inflammatory condition that can cause multi-organ dysfunction, characterized by high morbidity and mortality. Several therapies have been employed to target this disorder; however, few happen to be effectively employable even in the early phase. PFKFB3(6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-3) is a critical regulator of glycolysis and is upregulated under inflammatory, mitogenic, and hypoxia conditions. Essential information on the targeting of the inflammatory pathway will present the termination of the disorder and recovery. Herein we investigated the protective function of KAN0438757, a potent inhibitor of PFKFB3, and its mechanism of impeding AP induced in mice. KAN0438757 was confirmed to activate the Nrf2/HO-1 inflammatory signaling pathways in response to caerulein induced acute pancreatitis (CAE-AP) and fatty acid ethyl ester induced severe acute pancreatitis (FAEE-SAP). Additionally, KAN0438757 alleviated the inflammatory process in infiltrated macrophage via the Nrf2/HO-1 inflammatory signaling pathway and demonstrated a significant effect on the growth of mice with induced AP. And more importantly, KAN0438757 displayed negligible toxicity in vivo. Taken together our data suggest KAN0438757 directly suppresses the inflammatory role of PFKFB3 and induces a protective role via the Nrf2/HO-1 pathway, which could prove as an excellent therapeutic platform for SAP amelioration. [Display omitted] • KAN0438757 alleviated the inflammatory process in infiltrated macrophages. • KAN0438757 demonstrates negligible toxicity in vivo. • KAN0438757 suppresses the inflammatory role of PFKFB3. • KAN0438757 induces a protective role via the Nrf2/HO-1 pathway. [ABSTRACT FROM AUTHOR]

Magnetically separable catalysts were prepared and employed for the epoxidation of olefins with hydrogen peroxide. In all cases the magnetic core was firstly covered with a silica layer to prevent iron ion-initiated decomposition of hydrogen peroxide. The catalytic active species, an ionic liquid-type peroxotungstate, was then immobilized either by hydrogen bonding (catalyst 1) or by covalent SiO linkage (catalyst 2). In addition to a thorough characterization by FT-IR, XRD, NMR, DRIFT, XPS, and TEM, the catalytic potential was evaluated in the epoxidation of a variety of olefins as well as allylic alcohols. Both catalysts showed essentially a constant activity after at least ten consecutive cycles. On the basis of the research above, a new type of magnetically separable catalyst was constructed by immobilization of lacunary-type phosphotungstate by hydrogen bonding between the sulfonate anion and silanol group on the surface of the core-shell magnetic nanoparticles. After the detailed characterization, the catalyst was used in the epoxidation of a variety of olefins and allylic alcohols and was found to possess high activity, selectivity towards epoxides, and a constant activity after at least ten catalytic recycles without solvent. [ABSTRACT FROM AUTHOR]