Human MDFI blocking peptide

MyoD family inhibitor (MDFI) and MDFI domain-containing (MDFIC) are homologous proteins known to regulate myogenic transcription factors. Hitherto, their role in cancer is unknown. We discovered that MDFI is up- and MDFIC downregulated in colorectal tumors. Mirroring these different expression patterns, MDFI stimulated and MDFIC inhibited growth of HCT116 colorectal cancer cells. Further, MDFI and MDFIC interacted with Jumonji C domain-containing (JMJD) 1 A, a histone demethylase and epigenetic regulator involved in colorectal cancer. JMJD1A influenced transcription of several genes that were also regulated by MDFI or MDFIC. Notably, the HIC1 tumor suppressor gene was stimulated by JMJD1A and MDFIC, but not by MDFI, and HIC1 overexpression phenocopied the growth suppressive effects of MDFIC in HCT116 cells. Similar to colorectal cancer, MDFI was up- and MDFIC downregulated in breast, ovarian and prostate cancer, but both were overexpressed in brain, gastric and pancreatic tumors that implies MDFIC to also promote tumorigenesis in certain tissues. Altogether, our data suggest a tumor modulating function for MDFI and MDFIC in colorectal and other cancers that may involve their interaction with JMJD1A and a MDFIC -> HIC1 axis.

Microbicidal activity is related to the production of reactive oxygen species (ROS) that can be measured by flow-cytometry using rhodamine 123 (R123). Few assays have been proposed to measure ROS production, usually on heparinized samples but none of them.is standardized. Here we propose to improve the test by selecting poly-morphonuclears (PMN) and monocytes, labelled and activated in one step to keep the test short, and to standardize the process even between different systems (i.e. Navios (TM) and FACSCanto (TM)) using fluorescence intensity target setting ("FITS"). We applied this test on 15 patients without inflammation, 19 patients from an intensive care unit (ICU) and 11 healthy volunteers. Results: Provided calcium restitution, we show that the test can be performed on EDTA that is a better sample preservative. The results were highly correlated between instruments (r(2) = 0.898). PMN CD16 (and not CD14) expression was altered under stimulation with E. coli (MdFI = 239.3 +/- 93.5) or PMA (139.7 +/- 76.8) as compared to resting sample (307.6 +/- 145.1). RH123 was strongly and homogeneously induced by PMA (14.2 +/- 6.6) and more heterogeneously by E. coli (MdFI 21.9 +/- 23.4) as compared to unstimulated PNN (0.9 +/- 13,p < 0.0001). The test is useful not only for genetic disorders but also for secondary deficiencies as observed in ICU (E. coli RH123 MEI = 10.5 +/- 11.1 patients vs 30.1 +/- 26.5 in healthy donors). In ICU, CD16 expression was already altered on unstimulated samples (MdFI = 197.4 +/- 1312 vs 418, 2 +/- 813 in healthy donors; p 0.0001). Bacterial stimulation was dependent of the complement that partly explains deficiency to bacterial stimulus in ICU patients. (C) 2016 Published by Elsevier B.V.