BUB1 Promotes Gemcitabine Resistance in Pancreatic Cancer Cells by Inhibiting 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.

KAN0438757, a novel PFKFB3 inhibitor, prevent the progression of severe acute pancreatitis via the Nrf2/HO-1 pathway in infiltrated macrophage.

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.

A Systematic Review of Anogenital Distance and Gynecological Disorders: Endometriosis and Polycystic Ovary Syndrome.

Background and Aim: Anogenital distance (AGD) can serve as a life-long indicator of androgen action in gestational weeks 8-14. AGD has been used as an important tool to investigate the exposure to endocrine-disrupting compounds in newborns and in individuals with male reproductive disorder. Endometriosis and polycystic ovary syndrome (PCOS) are two common gynecological disorders and both are related to prenatal androgen levels. Therefore, we performed a systematic review to evaluate the relationships of AGD with these gynecological disorders. Methods: PubMed, Web of Science, and Embase were searched for published studies up to January 25, 2021. No language restriction was implemented. Results: Ten studies were included in this review. Five focused on women with endometriosis, and six investigated women with PCOS. According to these studies, PCOS patients had longer AGD than controls, while endometriosis patients had shorter AGD than controls. In conclusion, this study provides a detailed and accurate review of the associations of AGD with endometriosis and PCOS. Conclusion: The current findings indicate the longer AGD was related to PCOS and shorter AGD was related to endometriosis. However, further well-designed studies are needed to corroborate the current findings.

Ionic liquid immobilized nickel(0) nanoparticles as stable and highly efficient catalysts for selective hydrogenation in the aqueous phase.

Nickel nanoparticles (NPs) well-dispersed in the aqueous phase were conveniently prepared by reducing nickel(II) salt with hydrazine in the presence of the functionalized ionic liquid 1-(3-aminopropyl)-2,3-dimethylimidazolium bromide. UV/Vis spectroscopy, elemental analysis, thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS) show the presence of a weak interaction of the functionalized ionic liquid with Ni(II) and Ni(0) complexes. The face-centered cubic structure of the Ni(0) NPs was confirmed by X-ray diffraction (XRD) characterization. Transmission electron microscopy (TEM) images reveal that smaller Ni(0) particles of approximately 6-7 nm average diameter assemble to give larger, blackberry-shaped particles with an average diameter of around 35 nm. The Ni NPs were employed as highly efficient catalysts for the selective hydrogenation of C=C double bonds in the aqueous phase under mild reaction conditions (40-90 degrees C at 1.0-3.0 MPa), and the Ni(0) nanocatalysts in the aqueous phase are stable enough to be reused at least seven times without significant loss of catalytic activity during subsequent reuse cycles.