It is also not clear whether a low dose delivered to a larger volume in intensity modulated plans compared with simpler plans might reduce the possibility of a compensatory increase in kidney function. Nevertheless, a decrease in relative function of the irradiated kidney concurrent with a reduction in global renal function is probably a reasonable indicator of accumulating renal dysfunction. In summary, this report provides important evidence that radiation nephropathy can be predicted Inhibitors,research,lifescience,medical a priori based on dosimetric parameters and can be documented early using scintigraphic and biochemical
parameters. In the absence of either conclusive and validated dosimetric parameters or pharmacologic radiation mitigators/protectors, the primary driver in regards to sparing renal toxicity is the clinical judgment of the treating physician. The data presented here will serve to guide the treating physician. Footnotes No conflicts of interest.
The synthesis, processing and action of microRNAs is simplistically depicted in figure 1. Functionally Inhibitors,research,lifescience,medical active microRNAs, or mature microRNAs, are 18-22 nucleotide-long, single-stranded RNA molecules with 5′ phosphate and 3′ hydroxyl groups. A nascent mature microRNA, however, arises in pair as a double-stranded Inhibitors,research,lifescience,medical RNA molecule known as a microRNA/microRNA-star (*) duplex from a single precursor RNA (pre-microRNA). Pre-microRNAs are ~60-80 nucleotide-long with
a hairpin-like stem-loop secondary structure. Endoribonulease activity of a cytoplasmic RNAse III enzyme, Dicer, causes the release of the microRNA/microRNA* duplex-bearing stems from the stem-loop structures of pre-microRNAs. Pre-microRNAs
themselves are generated Inhibitors,research,lifescience,medical in the nucleus by the action of another RNAse III endoribonuclease, Drosha, on much longer, primary RNA molecules (pri-microRNAs) that are transcribed by RNA polymerases II and III from microRNA-encoding genes (6), (7). Two nucleotide-long 3′ overhangs on pre-microRNAs are recognized by the Exportin 5 transporter protein which shuttles them into the cytoplasm (8). Many other proteins are involved in this pathway for microRNA genesis. They include the Inhibitors,research,lifescience,medical Sodium butyrate Ran guanosine triphosphatase, which participates in the nuclear export of pre-microRNAs, and the double-stranded RNA-binding proteins DGCR8 (DiGeorge critical Selleckchem SB202190 region 8) and TRBP (transactivating response RNA binding protein), which work alongside Drosha and Dicer, respectively. Though most microRNAs arise in this framework, exceptions have been observed. For instance, maturation of microRNA miR-451 does not require the Dicer-mediated cleavage (9), and the precursor of microRNA miR-1234 is actually an intron (a ‘mirtron’) that is spliced out of the mRNA of a protein-coding gene (10). The sequences of mature microRNAs can get modified through 3’ uridylation or adenylation, or nucleotide substitution, with possible effects on their turnover as well as function (11). Figure 1.