Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation

Toxicity of aggregation-prone proteins is thought to play an important role in aging and age-related neurological diseases like Parkinson and Alzheimer's diseases. Here, we identify tryptophan 2,3-dioxygenase (tdo-2), the first enzyme in the kynurenine pathway of tryptophan degradation, as a metabolic regulator of age-related α-synuclein toxicity in a Caenorhabditis elegans model. Depletion of tdo-2 also suppresses toxicity of other heterologous aggregation-prone proteins, including amyloid-β and polyglutamine proteins, and endogenous metastable proteins that are sensors of normal protein homeostasis. This finding suggests that tdo-2 functions as a general regulator of protein homeostasis. Analysis of metabolite levels in C. elegans strains with mutations in enzymes that act downstream of tdo-2 indicates that this suppression of toxicity is independent of downstream metabolites in the kynurenine pathway. Depletion of tdo-2 increases tryptophan levels, and feeding worms with extra l-tryptophan also suppresses toxicity, suggesting that tdo-2 regulates proteotoxicity through tryptophan. Depletion of tdo-2 extends lifespan in these worms. Together, these results implicate tdo-2 as a metabolic switch of age-related protein homeostasis and lifespan. With TDO and Indoleamine 2,3-dioxygenase as evolutionarily conserved human orthologs of TDO-2, intervening with tryptophan metabolism may offer avenues to reducing proteotoxicity in aging and age-related diseases.     

Osteogenic potential of mesenchymal cells embedded in the provisional matrix after a 6-week healing period in augmented and non-augmented extraction sockets: an immunohistochemical prospective pilot study in humans

Purpose: The aim of the present clinical study was the evaluation of the osteogenic potential of mesenchymal cells embedded in the provisional matrix of non‐augmented and with Bio‐Oss collagen‐augmented human extraction sockets after 6 weeks of healing time. Methods: Twenty‐five patients with 47 extraction sites participated in the present study. After tooth removal, the extraction sockets were augmented with Bio‐Oss collagen or not augmented. At implant placement, bone biopsies of the extraction sockets were obtained. The immunohistochemical analysis of the osteogenic potential of the mesenchymal cells in the provisional matrix was performed using three monoclonal antibodies: core‐binding factor α1 (Cbfa1)/runt‐related protein (Runx)2, osteonectin (OSN/secreted protein acidic and rich in cyst [SPARC]) and osteocalcin (OC). The statistical analysis was performed using two‐factorial analysis for repeated measures, Mann–Whitney U‐test and Spearman's rank‐order correlation coefficient. Results: Of 47 extraction sockets examined, 17 sockets demonstrated an almost complete ossification. Hence, the provisional matrix of the 30 remaining extraction sockets (21 non‐augmented, 9 augmented) was immunohistochemically investigated. No evidence of acute or chronic inflammation was noted in any of the specimens. In the provisional matrix of the non‐grafted socket, the median amount of Cbfa1/Runx2‐positive cells was 72.3%, of OSN (SPARC) 66.9% and of OC 23.4%, whereas in the grafted sockets the median rate of immunopositive cells staining with Cbfa1/Runx2 was 73.3%, of OSN (SPARC) 61.4% and of OC 20.1%. There was no significant difference in the proportion of positive cells expressed by Cbfa1/Runx2, OSN/SPARC and OC between the grafted and non‐grafted socket. Furthermore, the cell density did not correlate to the quantity of stained cells independent of the used proteins. Discussion: After a 6‐week healing period, the provisional matrix was demonstrated to have a high proportion of cells displaying a maturation of mature osteoprogenitor cells to osteoblasts. The grafting procedure did not influence the quantity of osteogenic cells in the extraction socket. To cite this article:
Heberer S, Wustlich A, Lage H, Nelson JJ, Nelson K. Osteogenic potential of mesenchymal cells embedded in the provisional matrix after a 6‐week healing period in augmented and non‐augmented extraction sockets: an immunohistochemical prospective pilot study in humans.
Clin. Oral Impl. Res. 23 , 2012; 19–27.
doi: 10.1111/j.1600‐0501.2010.02148.x     

Clinical performance of a light-cured denture base material compared to polymethylmethacrylate—a randomized clinical study

The aim of this study was to evaluate the clinical long-term performance of a visible light-cured resin (VLCR) denture base material and to compare it to a well-established polymethylmethacrylate (PMMA)-based denture acrylic in a randomized split-mouth clinical long-term study. One hundred removable partial dentures in 90 patients, with at least two saddles each, were investigated. One saddle was made of VLCR, while the other was made of PMMA at random. Plaque adhesion, tissue reaction, and technical parameters of the dentures were assessed 6, 12, and 18 months after treatment. Statistical analysis was performed using the Wilcoxon rank-sum test. Though VLCR showed higher plaque adhesion than PMMA after 6, 12, and 18 months (p < 0.001), there were no important differences with regard to tissue reaction. Concerning plaque adhesion, surface quality with regard to the lower side, interfaces between denture acrylic and metal and the boundary between denture acrylic and denture tooth PMMA was rated higher than VLCR. The surface quality of the upper side of the denture saddles showed no significant differences (p > 0.05). Neither VLCR nor PMMA showed discoloration at any point in time (p > 0.05). It can be concluded that VLCR is a viable alternative for the production of removable dentures. Especially in patients with hypersensitivities to PMMA, VLCR is particularly suitable for clinical use.