Anti-E. coli Immunoglobulin Yolk (IgY): Reduction of pathogen receptors and inflammation factors could be caused by decrease in E. coli load.

Graft versus host disease (GVHD) remains the major cause of morbidity and mortality after allogeneic stem cell transplantation, especially for intestinal GVHD, as steroid resistant GVHD results in high mortality. For this reason, new treatments of GVHD are needed. One approach is the reduction of pathogenic bacteria using anti-E. coli Immunoglobulin Yolk (IgY). In a haploidentical murine model, B6D2F1 mice conditioned with total body irradiation (TBI), received bone marrow cells (BM) and splenocytes (SC) from either syngeneic (Syn = B6D2F1) or allogeneic (Allo = C57BL/6) donors. Following this, animals received from day -2 until day +28 chow contained IgY or control chow. Thereafter the incidence and severity of aGVHD, the cytokines, chemokines, IDO1 and different pathogen-recognition receptors (PRR) were analyzed and compared to control animals (received chow without IgY). We found that animals receiving chow with IgY antibody showed reduced GVHD severity compared to control animals. On day28 after alloBMT, IDO, NOD2, TLR2, TLR4 and the inflammatory chemokine CCL3, were reduced in the colon and correlated with a significant decrease in E. coli bacteria. In summary chow containing chicken antibodies (IgY) improved GVHD via decrease in bacterial load of E coli conducting to reduction of pathogen receptors (NOD2, TLR2 and 4), IDO, chemokines and cytokines.

The Impact of Nonsurgical Periodontal Therapy on Serum Levels of Dickkopf-Related Protein-1 in Smokers and Nonsmokers with Periodontitis: A Prospective Comparative Study.

Purpose: This study aimed to evaluate and compare Dickkopf-related protein-1 (DKK1) serum levels and periodontal clinical parameters of smokers and nonsmokers with periodontitis at baseline and after nonsurgical periodontal treatment. Patients and Methods: A prospective comparative study was conducted among 24 patients with periodontitis who were divided according to the smoking habits into two groups: nonsmokers (G1) and smokers (G2). All the participants were assessed clinically by recording the probing depth (PD), clinical attachment loss (CAL), plaque index (PI), and bleeding index (BI), and immunologically by measuring the DKK1 serum levels at baseline and six weeks after nonsurgical periodontal therapy. Results: The two groups showed a significant decrease in PI, BI, and CAL after periodontal therapy (p < 0.05), while PD was significantly reduced in G1 (p = 0.005). The PI mean value was significantly higher at the baseline in G2 versus G1 (p = 0.050), while PD, BI, and CAL values were not significantly different between the groups (p = 0.056, p = 0.241, and p = 0.381, respectively). For DKK1 serum levels, there was a statistically significant decrease after treatment compared to the baseline for both groups (G1: p < 0.001; G2: p < 0.001) but no significant difference before (p = 0.131) and six weeks after treatment (p = 0.334) between the two groups. Conclusion: Although nonsurgical periodontal treatment effectively improved periodontal clinical parameters and reduced DKK1 serum levels, there were no significant differences in the DKK1 serum levels among the smokers and nonsmokers with periodontitis.

Identification of PKHD1 mutations in Brain, Breast and Rectal tumors by Next Generation DNA Sequencing.

INTRODUCTION: It is well established that the PKHD1 mutations are associated with autosomal recessive polycystic kidney disease (ARPKD). Although, PKHD1 mutations are also detected in certain cancer types, to our knowledge in rare tumors such as, atypical teratoid rhabdoid tumor (ATRT), primary neuro-ectodermal tumor (PNET), atypicalchoroid plexus papilloma (a-CPP), amelanotic ano-rectal melanoma (AMM), and breast phyllodes tumors PKHD1 mutations profiling is not reported. METHODS: In order to determine the PKHD1 gene mutation patterns in the brain, rectal, and breast tumors we have analyzed these tumor DNA by Ion Proton Next generation DNA sequencing. RESULTS: Next-generation DNA sequencing on Ion Proton identified unique and common missense mutations in the brain, breast and ano-rectal tumors. All mutations were benign, and only one pathogenic mutation in p. (Cys3346Arg) found in AMM tumor. In phyllodes tumor of breast, two unique missense variants were detected (rs113562492) p. (Met2841Val); and (rs137972270) in p. (Arg589Cys) and these variants are not present in other tumors tested. The variant rs137972270 was reported only in two cases sofar in ClinVar database. Missense variants such as rs115045643, rs116809571, rs115338476, and rs76895755 are found only in PNET, and a variant rs62406032 in a-CPP, another one rs35445653 in ATRT cases were unique for these tumors, which are not present in other tumors. Several synonymous and intronic variants of PKHD1 gene were also found in these tumors. A synonymous variant p. (Asp395Asp), rs1896976 and two intronic SNPs viz., rs1326605, and rs1571084 were found in all tumors tested. The SNP rs9395699 in IVS66 was found uniquely in IPC breast tumor only in this study. Allele coverage, allele ratio, p-value, Phred qual score, sequencing coverage, alleles frequencies were also analysed, the p-values and Phred quality score were significantly higher. CONCLUSION: These tumors did not have any insertion/ deletion mutations, nonsense, or truncated mutations in it. The screening of PKHD1 gene revealed signature mutations for the solid tumors studied by NGS method. This investigation may help in understanding these tumor pathology at molecular level.

Effects of mineral trioxide aggregate, calcium hydroxide, biodentine and Emdogain on osteogenesis, Odontogenesis, angiogenesis and cell viability of dental pulp stem cells.

BACKGROUND: Vital pulp therapy preserves and maintains the integrity and the health of dental pulp tissue that has been injured by trauma, caries or restorative procedures. The enhancement of cells viability and formation of reparative dentine and new blood vessels are vital determinants of the success of direct pulp capping. Therefore, the aims of this study was to evaluate and compare the in vitro osteogenic, odontogenic and angiogenic effects of mineral trioxide aggregate (MTA), calcium hydroxide [Ca(OH)2], Biodentine and Emdogain on dental pulp stem cells (DPSCs) and examine the effects of the tested materials on cell viability. METHODS: DPSCs were treated with MTA, Ca(OH)2, Biodentine or Emdogain. Untreated cells were used as control. The cell viability was measured by MTT assay on day 3. Real-Time PCR with SYBR green was used to quantify the gene expression levels of osteogenic markers (alkaline phosphatase and osteopontin), odontogenic marker (dentin sialophosphoprotein) and angiogenic factor (vascular endothelial growth factor) on day 7 and day 14. RESULTS: All capping materials showed variable cytotoxicity against DPSCs (77% for Emdogain, 53% for MTA, 26% for Biodentine and 16% for Ca(OH)2 compared to control (P value < 0.0001). Osteopontin (OPN) and dentin sialophosphoprotein (DSPP) gene expression was increased by all four materials. However, alkaline phosphatase (ALP) was upregulated by all materials except Emdogain. Vascular endothelial growth factor (VEGF) expression was upregulated by all four tested materials except Ca(OH)2. CONCLUSIONS: Our results suggest MTA, Biodentine and Emdogain exhibit similar attributes and may score better than Ca(OH)2. Emdogain could be a promising alternative to MTA and Biodentine in enhancing pulp repair capacity following dental pulp injury. However, further future research is required to assess the clinical outcomes and compare it with the in vitro findings.