S100PBP is regulated by mutated KRAS and plays a tumour suppressor role in pancreatic cancer.

We have previously shown that expression of S100PBP, an S100P binding partner, gradually decreases during progression of pancreatic ductal adenocarcinomas (PDAC). Here, we show that loss of S100PBP leads to oncogenic transformation of pancreatic cells; after deregulation of S100PBP expression, both in silico and in vitro analyses highlighted alterations of genes known to modulate cytoskeleton, cell motility and survival. Overexpression of S100P reduced S100PBP expression, while co-immunoprecipitation indicated the interaction of S100P with S100PBP-p53-ubiquitin protein complex, likely causing S100PBP degradation. The doxycycline-induced KrasG12D activation resulted in decreased S100PBP levels, while low-dose treatment with HDAC inhibitor MS-275 rescued its expression in both human and mouse PDAC cell lines. This indicates KrasG12D as an upstream epigenetic regulator of S100PBP. Finally, analysis of TCGA PanCancer Atlas PDAC datasets demonstrated poor prognosis in patients with high S100P and low S100PBP expression, suggesting that S100PBP is a novel tumour suppressor gene with potential clinical utility.

Oxidative stress and motility impairment in the semen of fertile males.

The aim of the study was to determine the total oxidant status (TOS) and evaluate the influence of oxidative stress on sperm quality in fertile males. The study population consisted of 55 fertile males. Based on the seminal plasma TOS value, the study subjects were divided into the two subgroups: a group with a low (TOS-L) and a high (TOS-H) value. Comparing the TOS-H group with the TOS-L group, we found poorer sperm motility in the TOS-H group. We found lower total antioxidant capacity values and lower activity levels in the majority of the determined superoxide dismutase, glutathione peroxidase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase. Further, we found higher levels of copper and iron as well as lower levels of zinc in the TOS-H group. We observed lower medians of IL-2, 4, 6, 8 and INF-γ in the TOS-H group compared with the TOS-L group, whereas the medians of IL-1ß, IL-10 and IL-12 were significantly higher. In fertile males, higher oxidative stress intensity was associated with poorer semen quality and decreased antioxidant capacity in semen. These negative effects might be a result of decreased activities of antioxidant enzymes and altered levels of trace metals and cytokines.