Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis

The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis.

Biocompatibility evaluation of an antibiotic paste after pulpotomy in dogs

The purpose of this study was to evaluate by histological analysis, the biocompatibility of an antibiotic paste following treatment of pulpotomies in dogs. Four male adult dogs were used and their mandibular and maxilar premolars and molars (PM3; PM4; M1; PM4;M1) of both sides were submitted to pulpotomies. The antibiotic paste (CTZ) was prepared with chloramphenicol, tetracycline, zincoxide and eugenol. After 6, 8, 9 and 10 months post-pulpotomy the dogs were sacrificed. Histological analysis of the teeth revealed an intense inflammatory process in the coronal pulp at 6 months after pulpotomy, with inflammatory cells dispersed throughout the entireapical region in this period. This process became partially reduced at 8 and 9 months after pulpotomy, and totally disappeared by the end of the experiment, at 10 months. In conclusion, the endodontic treatment with this antibiotic paste seemed to be biocompatible under the present experimental conditions. However, further clinical studies are necessary to assure that this paste is safe for use in pulpotomies in children.