Plithotaxis, a collective cell migration, regulates the sliding of proliferating pulp cells located in the apical niche.

Using the proliferating cell nuclear antigen (PCNA) immunostaining, we previously identified, after pulp exposure, three zones of proliferating cells in the rat molar pulp. Zones I and II were in the crown near the pulp. Zone III was near the apex revealing a recruitment of mitotic cells at distance from the lesion. To gain further insight into the spatio-temporal evolution of proliferating pulp cells of zone III, we performed a longitudinal study of PCNA staining in rat molar mesial root at 3, 8, and 15 d after pulp exposure associated to implantation of unloaded or amelogenin loaded agarose beads. At day 3 after implantation, PCNA-positive cells were located in the central part of the radicular pulp. At day 8, PCNA-labeled cells were aligned in the lateral part of the pulp beneath the odontoblast/sub-odontoblast layer. At day 15, PCNA labeling became undetectable in the root and was located in the coronal pulp. These results suggest that after pulp exposure, PCNA-positive cells may migrate from the central part of the radicular pulp to the sub-odontoblast cell layer and then from the apical root to the crown. Electron microscopy and immunostaining analysis showed that pulpal cells were linked by desmosome-like and gap-junctions. Extracellular matrix was composed of thin collagen fibrils associated with glycosaminoglycans favoring cell mobility. These data suggest that the syncytium-like structure formed by pulp radicular cells may be a pre-request for plithotaxis, a collective cell migration process. This emergent mechanism may govern pulp healing and regeneration after dental lesion.

Pharmacological Modulation of Temporal Discounting: A Systematic Review.

Temporal discounting is a phenomenon where a reward loses its value as a function of time (e.g., a reward is more valuable immediately than when it delays in time). This is a type of intertemporal decision-making that has an association with impulsivity and self-control. Many pathologies exhibit higher discounting rates, meaning they discount more the values of rewards, such as addictive behaviors, bipolar disorder, attention-deficit/hyperactivity disorders, social anxiety disorders, and major depressive disorder, among others; thus, many studies look for the mechanism and neuromodulators of these decisions. This systematic review aims to investigate the association between pharmacological administration and changes in temporal discounting. A search was conducted in PubMed, Scopus, Web of Science, Science Direct and Cochrane. We used the PICO strategy: healthy humans (P-Participants) that received a pharmacological administration (I-Intervention) and the absence of a pharmacological administration or placebo (C-Comparison) to analyze the relationship between the pharmacological administration and the temporal discounting (O-outcome). Nineteen studies fulfilled the inclusion criteria. The most important findings were the involvement of dopamine modulation in a U-shape for choosing the delayed outcome (metoclopradime, haloperidol, and amisulpride). Furthermore, administration of tolcapone and high doses of d-amphetamine produced a preference for the delayed option. There was a time-dependent hydrocortisone effect in the preference for the immediate reward. Thus, it can be concluded that dopamine is a crucial modulator for temporal discounting, especially the D2 receptor, and cortisol also has an important time-dependent role in this type of decision. One of the limitations of this systematic review is the heterogeneity of the drugs used to assess the effect of temporal discounting.

Circulating miR-141-3p, miR-143-3p and miR-200c-3p are differentially expressed in colorectal cancer and advanced adenomas.

Colorectal cancer (CRC) is one of the prominent causes of cancer related deaths because, in part, there is not an early, non-invasive, effective detection strategy. Circulating microRNAs (miRNAs) have been proposed as potential non-invasive biomarkers for CRC. In this study, we evaluated the miRNA profile in sixteen CRC tissues by Next-Generation-Sequencing and compared the circulating expression levels of 22 miRNAs among 45 CRC, 14 hyperplastic polyps, 11 advanced adenoma patients and 45 control subjects, by reverse transcription-quantitative PCR, to search for miRNAs which could be potential biomarkers. In total, nine of them represented 70% of total read counts (miR-10a-5p, miR-192-5p, miR-10b-5p, miR-22-3p, miR-26a-5p, miR-148a-3p, miR-181a-5p, miR-92a-3p and miR-143-5p). In silico analysis found eight candidates to mature miRNAs. With respect to circulating miRNA, we found higher serum expression levels of miR-143-3p, miR-141-3p and miR-200c-3p in the CRC and adenoma groups compared with controls (P<0.002), and we also found significant higher levels of miR-141-3p and miR-200c-3p in serum of adenoma patients compared with the CRC group. In conclusion, the measurement of miRNAs in the blood could complement current screening methods for CRC and might provide new insights into mechanisms of tumorigenesis. miR-143-3p, miR-141-3p and miR-200c-3p could be interesting miRNAs to study as potential biomarkers for CRC.