P2X receptors in maintenance and differentiation of neural progenitor cells

<正>Purinergic receptors are among the first cell surface receptors expressed during embryonic development(Burnstock and Ulrich,2011).These are characterized based on their pharmacological properties of being activated by adenosine or purine/pyrimidine nucleotides as P1 and P2 receptors.P2receptors are further classified by their structure as P2Y metabotropic and P2X ionotropic receptors.P2Y receptors in mammalians consist of P2Y1,2,4,6,11,12 and 14 subtypes,     

From positive emotionality to internalizing problems: the role of executive functioning in preschoolers

Temperament and psychopathology are intimately related; however, research on the prospective associations between positive emotionality, defined as a child’s positive mood states and high engagement with the environment, and psychopathology is inconclusive. We examined the longitudinal relation between positive emotionality and internalizing problems in young children from the general population. Furthermore, we explored whether executive functioning mediates any observed association. Within a population-based Dutch birth cohort, we observed positive emotionality in 802 children using the laboratory temperament assessment battery at age 3 years. Child behavior checklist (CBCL) internalizing problems (consisting of Emotionally Reactive, Anxious/Depressed, and Withdrawn scales) were assessed at age 6 years. Parents rated their children’s executive functioning at ages 4 years. Children with a lower positive emotionality at age 3 had a higher risk of withdrawn problems at age 6 years (OR = 1.20 per SD decrease in positive emotionality score, 95 % CI: 1.01, 1.42). This effect was not explained by preexisting internalizing problems. This association was partly mediated by more problems in the shifting domain of executive functioning (p < 0.001). We did not find any relation between positive emotionality and the CBCL emotionally reactive or anxious/depressed scales. Although the effect sizes were moderate, our results suggest that low levels of positive emotionality at preschool age can result in children’s inflexibility and rigidity later in life. The inflexibility and rigidity are likely to affect the child’s drive to engage with the environment, and thereby lead to withdrawn problems. Further research is needed to replicate these findings.     

Biology-Driven Approaches to Prevent and Treat Relapse of Myeloid Neoplasia after Allogeneic Hematopoietic Stem Cell Transplantation

The curative potential of allogeneic hematopoietic cell transplantation (allo-HCT) in the treatment of acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) relies mainly on the graft-versus-leukemia effect. Relapse after allo-HCT occurs in a considerable proportion of patients and has a dismal prognosis, with still very limited curative potential. This review provides an overview of the established and evolving approaches to preventing or treating relapse of AML and MDS after allo-HCT, in the context of novel insight into the biology of relapse. Established prophylactic measures to prevent relapse include optimized conditioning and graft-versus-host disease (GVHD) prophylaxis, as well as donor lymphocyte infusion (DLI) for high-risk patients; novel immunomodulatory interventions and maintenance approaches are still experimental. Improved diagnostics can detect persistent or recurring disease at a molecular level, enabling early preemptive interventions. Established options include hypomethylating agents and DLI. Standard treatments for hematologic relapse include chemotherapy, cessation of immunosuppressive treatment, and DLI. Experimental approaches include molecular targeted therapies, novel immunomodulatory treatments, and second allo-HCT. For all interventions, the potential risks, including occurrence of GVHD, must be weighed against the benefits individually in each patient. Concurrently, prevention and treatment of relapse after allo-HCT remain challenging and unmet medical needs.     

Immunohistochemical and clinical evaluation of cathepsin expression in soft tissue sarcomas

Lysosomal proteases are known to enhance the spread of epithelial tumour cells, but little is known of the possible role of proteases in the growth of soft tissue sarcomas (STS). We investigated the expression of cathepsins D, B, S, H, L and procathepsin L in frozen sections of 34 STS from 34 patients by immunohistochemistry (IHC). Cathepsins D, B and H were relatively highly expressed in STS (77–91%). The expression rate of cathepsins S and L and of procathepsin L was lower (40–66%). Cathepsin S and L expression showed a moderate (P = 0.078 andP = 0.019) and procathepsin L a strong (P = 0.00001) correlation with the survival rate of STS patients. Cathepsin S expression is also correlated with the local recurrence rate (P < 0.01). Lysosomal proteases may play a role in STS progression, and cathepsin expression may also have, significance as a prognostic factor in STS.     

Vascularity for healing of meniscus repairs

Vascularity in the human meniscus is poor beyond 1-2 mm from the meniscosynovial junction, yet 22% of the tears in this series occur with a greater than or equal to 3-mm peripheral white rim. It is possible to suture these tears with the wider peripheral white rims, but healing rates are reduced because it is more difficult to obtain a satisfactory vascular supply. This article describes the history of our efforts at obtaining blood supply for healing of meniscus tears with a peripheral white rim up to 5 mm. Resection of the peripheral white rim to the vascular bed was unsatisfactory because it reduced the size of the meniscus and, by 3 years, the subsequent degenerative changes in the knee were comparable to meniscectomy. Holes made in the rim with a biopsy needle were again unsuccessful at improving healing. The present technique involves using rasps to abrade the parameniscal synovium on both the superior and inferior surface of the peripheral white rim. None of the peripheral white rim is resected. In the first series of 240 patients in whom peripheral white rim resection or the biopsy punch was used, the failure rate of meniscus healing was 22%. In a subsequent series of 68 patients (52 males, 16 females) who had 81 meniscal repairs by means of the rasp for parameniscal synovial abrasion, the failure rate was 9%. The rasp appears to be the safest and most effective method to gain vascularity for healing of meniscus repairs. It is possible to obtain healing with 5-mm peripheral white rims without resection of any portion of this rim, thus maintaining the full size of the meniscus.