High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instability

High-level microsatellite instability (MSI-H) in colorectal cancer accounts for about 12% of colorectal cancers and is typically associated with a dense infiltration with cytotoxic CD8-positive lymphocytes. The role of regulatory T cells that may interfere with the host's antitumoural immune response in MSI-H colorectal cancers has not been analysed yet. Using an antibody directed against the regulatory T-cell marker transcription factor forkhead box P3 (FOXP3), regulatory T cells were examined in 70 colorectal cancers with known MSI status (MSI-H, n=37; microsatellite stable, n=33). In MSI-H colorectal cancers, we found a significantly higher intraepithelial infiltration with FOXP3-positive cells (median: 8.5 cells per 0.25 mm2 vs 3.1 cells per 0.25 mm2 in microsatellite stable, P<0.001), and a significantly elevated ratio of intraepithelial to stromal infiltration (0.05 vs 0.01 in microsatellite stable, P<0.001). CD8-positive cell counts were related positively to the number of FOXP3-positive cells (Spearman's ρ=0.56 and 0.55, respectively). Our results show that the elevated number of CD8-positive lymphocytes found in MSI-H colorectal cancers is paralleled by an enhanced infiltration with CD8-negative FOXP3-positive cells. These data suggest that FOXP3-positive cells may play a role in the regulation of the immune response directed against MSI-H colorectal cancers at the primary tumour site

Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis

Holoprosencephaly, bilateral cleft lip and palate and ectrodactyly: another case and follow up.

Item does not contain fulltextWe describe a male patient with lobar holoprosencephaly, ectrodactyly, and cleft lip/palate, a syndrome which has been seen previously in only six patients. In addition, our patient developed hypernatraemia, which has been described in three patients before

3D-printed barium strontium titanate-based piezoelectric scaffolds for bone tissue engineering

In order to promote bone healing, new generations of biomaterials are under development. These biomaterials should demonstrate proper biological and mechanical properties preferably similar to the natural bone tissue. In this research, 3D-printed barium strontium titanate (BST)/β-tricalcium phosphate (β-TCP) composite scaffolds have been synthesized as an alternative strategy for bone regeneration to not only induce appropriate bioactive characteristics but also piezoelectric behavior. The physical, chemical and biological performance of the scaffolds have been examined in terms of mechanical, dielectric properties, apatite-forming ability, Alizarin Red Staining (ARS), Alkaline Phosphatase activity (ALP), and cytotoxicity. The samples composed of 60 BST and 40 β-TCP showed the highest compressive strength, bending module, elastic modulus and the Young's modulus. The dielectric constant increased with further addition of the BST phase in the constructs. Scanning Electron Microscope (SEM) and energy dispersive X-ray (EDX) analyses showed that 60 BST/40 β-TCP sample had the highest amount of bone-like apatite formation after 28 days in simulated body fluid (SBF). Moreover, the results of ARS proved that 60 BST/40 β-TCP composite could present higher quantities of mineral deposition. The ALP activity of osteosarcoma cells on 60 BST/40 β-TCP sample showed higher activities compare with the other composites. None of the samples demonstrated any sign of toxicity using MTT test. It can be suggested that BST/β-TCP composite scaffolds can be potentially used as the next generation of bone tissue engineering scaffold materials. © 2019 Elsevier Ltd and Techna Group S.r.l

Molecular analysis of aniridia patients for deletions involving the Wilms' tumor gene

A human aniridia candidate (AN) gene on chromosome 11p13 has been cloned and characterized. The AN gene is the second cloned gene of the contiguous genes syndrome WAGR (Wilms' tumor, aniridia, genitourinary malformations, mental retardation) on chromosome 11p13, WT1 being the first gene cloned. Knowledge about the position of the AN and WT1 genes on the map of 11p13 makes the risk assessment for Wilms' tumor development in AN patients possible. In this study, we analyzed familial and sporadic aniridia patients for deletions in 11p13 by cytogenetic analyses, in situ hybridization, and pulsed field gel electrophoresis (PFGE). Cytogenetically visible deletions were found in 3/11 sporadic AN cases and in one AN/WT patient, and submicroscopic deletions were identified in two sporadic AN/WT patients and in 1/9 AN families. The exact extent of the deletions was determined with PFGE and, as a result, we could delineate the risk for Wilms' tumor development. Future analyses of specific deletion endpoints in individual AN cases with the 11p13 deletion should result in a more precise risk assessment for these patient

Am. J. Hum. Genet.

families with nonsyndromic X-linked mental retardation (NS-XLMR), >30% of mutations seem to cluster on proximal Xp and in the pericentric region. In a systematic screen of brain-expressed genes from this region in 210 families with XLMR, we identified seven different mutations in JARID1C, including one frameshift mutation and two nonsense mutations that introduce premature stop codons, as well as four missense mutations that alter evolutionarily conserved amino acids. In two of these families, expression studies revealed the almost complete absence of the mutated JARID1C transcript, suggesting that the phenotype in these families results from functional loss of the JARID1C protein. JARID1C (Jumonji AT-rich interactive domain 1C), formerly known as "SMCX," is highly similar to the Y-chromosomal gene JARID1D/SMCY, which encodes the H-Y antigen. The JARID1C protein belongs to the highly conserved ARID protein family. It contains several DNA-binding motifs that link it to transcriptional regulation and chromatin remodeling, processes that are defective in various other forms of mental retardation. Our results suggest that JARID1C mutations are a relatively common cause of XLMR and that this gene might play an important role in human brain function