Natriuretic Peptides in Post-mortem Brain Tissue and Cerebrospinal Fluid of Non-demented Humans and Alzheimer's Disease Patients

Pathophysiology, epidemiology and therapy of agein

Natriuretic Peptides in Post-mortem Brain Tissue and Cerebrospinal Fluid of Non-demented Humans and Alzheimer's Disease Patients

Pathophysiology, epidemiology and therapy of agein

Lrp5 Is Not Required for the Proliferative Response of Osteoblasts to Strain but Regulates Proliferation and Apoptosis in a Cell Autonomous Manner

Although Lrp5 is known to be an important contributor to the mechanisms regulating bone mass, its precise role remains unclear. The aim of this study was to establish whether mutations in Lrp5 are associated with differences in the growth and/or apoptosis of osteoblast-like cells and their proliferative response to mechanical strain in vitro. Primary osteoblast-like cells were derived from cortical bone of adult mice lacking functional Lrp5 (Lrp5−/−), those heterozygous for the human G171V High Bone Mass (HBM) mutation (LRP5G171V) and their WT littermates (WTLrp5, WTHBM). Osteoblast proliferation over time was significantly higher in cultures of cells from LRP5G171V mice compared to their WTHBM littermates, and lower in Lrp5−/− cells. Cells from female LRP5G171V mice grew more rapidly than those from males, whereas cells from female Lrp5−/− mice grew more slowly than those from males. Apoptosis induced by serum withdrawal was significantly higher in cultures from Lrp5−/− mice than in those from WTHBM or LRP5G171V mice. Exposure to a single short period of dynamic mechanical strain was associated with a significant increase in cell number but this response was unaffected by genotype which also did not change the ‘threshold’ at which cells responded to strain. In conclusion, the data presented here suggest that Lrp5 loss and gain of function mutations result in cell-autonomous alterations in osteoblast proliferation and apoptosis but do not alter the proliferative response of osteoblasts to mechanical strain in vitro

Syndecan-1 and FGF-2, but Not FGF Receptor-1, Share a Common Transport Route and Co-Localize with Heparanase in the Nuclei of Mesenchymal Tumor Cells

Syndecan-1 forms complexes with growth factors and their cognate receptors in the cell membrane. We have previously reported a tubulin-mediated translocation of syndecan-1 to the nucleus. The transport route and functional significance of nuclear syndecan-1 is still incompletely understood. Here we investigate the sub-cellular distribution of syndecan-1, FGF-2, FGFR-1 and heparanase in malignant mesenchymal tumor cells, and explore the possibility of their coordinated translocation to the nucleus. To elucidate a structural requirement for this nuclear transport, we have transfected cells with a syndecan-1/EGFP construct or with a short truncated version containing only the tubulin binding RMKKK sequence. The sub-cellular distribution of the EGFP fusion proteins was monitored by fluorescence microscopy. Our data indicate that syndecan-1, FGF-2 and heparanase co-localize in the nucleus, whereas FGFR-1 is enriched mainly in the perinuclear area. Overexpression of syndecan-1 results in increased nuclear accumulation of FGF-2, demonstrating the functional importance of syndecan-1 for this nuclear transport. Interestingly, exogenously added FGF-2 does not follow the route taken by endogenous FGF-2. Furthermore, we prove that the RMKKK sequence of syndecan-1 is necessary and sufficient for nuclear translocation, acting as a nuclear localization signal, and the Arginine residue is vital for this localization. We conclude that syndecan-1 and FGF-2, but not FGFR-1 share a common transport route and co-localize with heparanase in the nucleus, and this transport is mediated by the RMKKK motif in syndecan-1. Our study opens a new perspective in the proteoglycan field and provides more evidence of nuclear interactions of syndecan-1

Review of Matrix Metalloproteinases’ Effect on the Hybrid Dentin Bond Layer Stability and Chlorhexidine Clinical Use to Prevent Bond Failure

This review describes the relationship between dentin collagen hybrid bond layer degradation and the Matrix Metalloproteinases (MMPs) after their release by acid etch and rinse adhesives and self etching bonding adhesives that can reduce the bond stability over time. MMP-2, MMP-8 and MMP-9 are indicated as the active proteases that breakdown the collagen fibrils in the hybrid bond layer. Phosphoric acid in the acid etch and rinse bonding process and acid primers in the self etch process are implicated in the release of these proteases and their activation by several non-collagen proteins also released from dentin by the etching. MMPs are released in saliva by salivary glands, by cells in the gingival crevices to crevicular fluid and by pulpal odontoblasts cells to the dentinal fluids. These sources may affect the hybrid layer also. Evidence of the bond strength deterioration over time and the ability of Chlorhexidine to prevent bond deterioration by inhibiting MMP action are discussed. Dentin Bonding procedure utilizing Chlorhexidine for different application times and concentrations are being developed. The application of 2% Chlorhexidine to the phosphoric acid etch surface after rinsing off the acid is the only procedure that has been clinically tested for a longer period of time and shown to prevent bond strength degradation so far. The adoption of this procedure is recommended as means of improving bond stability at this time

Angiotensin II type I receptor autoantibodies and prostate cancer: cross-sectional and longitudinal studies.

Autoantibodies against the angiotensin II type I receptor (AT1R) have been associated with multiple diseases (pre-eclampsia, malignant hypertension, transplant rejection, Huntington’s and Alzheimer’s disease, ovarian cancer) suggesting that while the autoantibodies are not necessarily causative they may promote disease progression. These autoantibodies (AT1RaAbs) bind and chronically activate the receptor increasing inflammatory burden. The prostate has a local renin angiotensin system that has been implicated in prostate cancer growth. Two distinct datasets were used to examine the associations between AT1RaAbs and prostate cancer. A cross-sectional set (n = 151) consisting of 101 serum specimens that were collected from patients with scheduled appointments for either elevated prostate specific antigen levels, a scheduled prostate biopsy or being seen as a newly diagnosed PCA patient in a Urology Outpatient Clinic. 80 of these patients were positive for PCA at biopsy, whereas 21 were biopsy benign (either atrophy, benign prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia or inflammation). The remaining 50 specimens were collected from men visiting an offsite prostate cancer screening who were free of prostate disease. Comparisons of covariate values between groups were by Kruskal-Wallis ANOVA with Dunn’s multiple comparisons test. Pairwise correlations between AT1RaAb and clinical correlates or pathological measurements were assessed using Spearman rank correlations. The longitudinal set of pre-diagnosis serum samples from 109 men was obtained from the Baltimore Longitudinal Study of Aging. This prospective cohort study is run by the National Institute on Aging, National Institutes of Health. Clinical measures associated with each BLSA serum sample include age, BMI, blood pressure, PSA levels and, for subjects who later developed PCA, the diagnosis date. All serum is from subjects now deceased with known date of death and post-mortem pathological status of the prostate (disease-free or PCA present). Time to events (diagnosis or death) were modeled nonparametrically by Kaplan-Meier survival curves, dichotomizing samples into either low or high AT1RaAb levels and analyzing serum samples grouped as most proximal or distal to timed event. Accelerated failure estimates were used to assess the effects of other predictors on AT1RaAb association with disease-free and overall survival at most proximal or most distal time points. The datasets correspond to the a study described in the Journal of Translational Autoimmunity published online 13 August 2019, 10000. "Angiotensin receptor autoantibodies as exposures that modify disease progression: cross sectional, longitudinal and in vitro studies of prostate cancer." https://doi.org/10.1016/j.jtauto.2019.10000

Data Set and Methods for Association of Angiotensin Receptor Autoantibodies with Abnormal Cardiovascular Abnormalities in Preeclampsia

This dataset is associated with an article entitled "Association of Angiotensin Receptor Autoantibodies with Cardiovascular Abnormalities in Preeclampsia." The text describes a study of a prospective cohort of women with preeclampsia with severe features of preeclampsia and controls. Twenty-one women with prior preeclampsia and twenty normotensive controls underwent evaluation at recruitment and at 4-year follow-up. A subset of 12 women with preeclampsia and 12 controls underwent echocardiography and had their serum levels of an angiotensin II type I receptor autoantibody measured by a quantitative antigen capture immunoassay at the same time. A subset of 12 women with preeclampsia and 12 controls underwent echocardiography 4 years postpartum and were similarly evaluated. The associations between the autoantibody levels and demographics, echocardiographic indices of diastolic dysfunction and with incident hypertension were determined