Osteopontin phosphopeptide mitigates calcium oxalate stone formation in a Drosophila melanogaster model.

Kidney stone disease affects nearly one in ten individuals and places a significant economic strain on global healthcare systems. Despite the high frequency of stones within the population, effective preventative strategies are lacking and disease prevalence continues to rise. Osteopontin (OPN) is a urinary protein that can inhibit the formation of renal calculi in vitro. However, the efficacy of OPN in vivo has yet to be determined. Using an established Drosophila melanogaster model of calcium oxalate urolithiasis, we demonstrated that a 16-residue synthetic OPN phosphopeptide effectively reduced stone burden in vivo. Oral supplementation with this peptide altered crystal morphology of calcium oxalate monohydrate (COM) in a similar manner to previous in vitro studies, and the presence of the OPN phosphopeptide during COM formation and adhesion significantly reduced crystal attachment to mammalian kidney cells. Altogether, this study is the first to show that an OPN phosphopeptide can directly mitigate calcium oxalate urolithiasis formation in vivo by modulating crystal morphology. These findings suggest that OPN supplementation is a promising therapeutic approach and may be clinically useful in the management of urolithiasis in humans.

Vasorelaxing cell permeant phosphopeptide mimetics for subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) due to rupture of an intracranial aneurysm leads to vasospasm resulting in delayed cerebral ischemia. Therapeutic options are currently limited to hemodynamic optimization and nimodipine, which have marginal clinical efficacy. Nitric oxide (NO) modulates cerebral blood flow through activation of the cGMP-Protein Kinase G (PKG) pathway. Our hypothesis is that SAH results in downregulation of signaling components in the NO-PKG pathway which could explain why treatments for vasospasm targeting this pathway lack efficacy and that treatment with a cell permeant phosphopeptide mimetic of downstream effector prevents delayed vasospasm after SAH. Using a rat endovascular perforation model, reduced levels of NO-PKG pathway molecules were confirmed. Additionally, it was determined that expression and phosphorylation of a PKG substrate: Vasodilator-stimulated phosphoprotein (VASP) was downregulated. A family of cell permeant phosphomimetic of VASP (VP) was wasdesigned and shown to have vasorelaxing property that is synergistic with nimodipine in intact vascular tissuesex vivo. Hence, treatment targeting the downstream effector of the NO signaling pathway, VASP, may bypass receptors and signaling elements leading to vasorelaxation and that treatment with VP can be explored as a therapeutic strategy for SAH induced vasospasm and ameliorate neurological deficits.

The Role of Diet in Osteoporotic Fracture Healing: a Systematic Review.

PURPOSE OF REVIEW: Summarize the in vivo evidences on the association between nutrition and osteoporosis fracture healing. RECENT FINDINGS: Osteoporotic fractures constitute a considerable public health burden. The healing capacity of fractures is influenced by local factors related to the fracture and by general factors (e.g., age, sex, osteoporosis, muscular mass, smoking, alcohol, drugs, and diet). The systematic review was conducted according to PRISMA statement. From the literature search on PubMed and Web of Science, from January 2016 to October 2019, twelve studies were selected and resulted highly variable in samples, exposure, methods, outcomes, and outcome assessment. Eleven studies were conducted on laboratory animals. Only one study aimed to investigate the impact of nutritional status on fracture healing in osteoporotic patients. In this review, the role of calcium/vitamin D supplementation remained controversial, while sialoglycoprotein supplementation, phytoestrogen-rich herb extract, flavonoids, and phosphorylated peptides showed a positive effect on osteoporotic fracture healing.

Does systemic administration of casein phosphopeptides affect orthodontic movement and root resorption in rats?

OBJECTIVES: To assess the potential effects of casein phosphopeptides (CPPs) on orthodontically induced iatrogenic root resorption (OIIRR) and orthodontic teeth movement. MATERIALS AND METHODS: Forty Wistar rats (aged 11 weeks) were randomly divided into experimental group (EG; n = 20) that received a diet supplemented with CPP and control group (CG; n = 20) devoid of diet supplement. A 150 g force was applied using nickel titanium (NiTi) coil that was bonded on maxillary incisors and extended unilaterally to a maxillary first molar. At Day 28, animals in both groups were euthanized. Volumetric assessment of root resorption craters and linear measurement of maxillary first molars movement were blindly examined using a micro-computed tomography scan. RESULTS: Nine rats were excluded from the experiment due to loss during general anesthesia or appliances' failure. Intra-operator reproducibility was high in both volumetric and linear measurements, 92.8 per cent and 98.5-97.6 per cent, respectively. The results reveal that dietary CPP has statistically insignificant effect on the overall OIIRR and orthodontic movement. CONCLUSIONS: CPP seems to have statistically insignificant effect on the volume of OIIRR and orthodontic movement in rats. A long-term study with larger sample size using a different concentration of CPP is required to clarify the dentoalveolar effect of CPP.

Engineering phosphopeptide-decorated magnetic nanoparticles as efficient photothermal agents for solid tumor therapy.

Due to the high therapeutic efficiency and minimum damage towards normal tissues, phototherapy has drawn a great deal of attention in recent decades. Herein, we reported the synthesis of novel phosphopeptide-decorated magnetic nanoparticles (peptide-Fe3O4 nanoparticles), and their usages in photothermal therapy against solid tumor. By using a classical coprecipitation method and a facile ligand exchange route, these peptide-Fe3O4 nanoparticles were prepared with inexpensive inhesion. Upon the irradiation of a near-infrared (NIR) light, these nanoagents exhibited great photothermal effect with high photo-stability. In vitro biocompatibility studies of these peptide-Fe3O4 nanoparticles indicated their low cytotoxicity, negligible hemolysis, and no effect on blood coagulation. As expected, 4T1 murine breast cancer cells could be effectively damaged by these light-mediated nanoagents. Significantly, animal experiments demonstrated that these nanoagents held great solid tumor ablation effect with the assistance of a NIR laser irradiation. Additional studies focused on the long-term toxicity of these nanoagents indicated their high bio-compatibility. Thus, these peptide-Fe3O4 nanoparticles could bring more opportunities to a new generation of photothermal agents in the field of biomedicine.

Effect of casein phosphopeptide and 25-hydroxycholecalciferol on tibial dyschondroplasia in growing broiler chickens.

1. An experiment was conducted to investigate the influence of dietary casein phosphopeptides and 25-hydroxycholecalciferol on the incidence of tibial dyschondroplasia (TD) in 14-d-old commercial broiler chickens. 2. Three hundred and twenty broiler chicks (one day old) were randomly allocated to one of 4 dietary treatments. A standard broiler diet was used as the control with the three experimental treatments receiving the control diet supplemented with 10 g casein phosphopeptide/kg, 14 g casein phosphopeptide/kg or 69 microg 25-hydroxycholecalciferol/kg. 3. Those birds fed the diets supplemented with 14g casein phosphopeptide/kg or 25-hydroxycholecalciferol had a lower incidence of TD than both the control and 10g casein phosphopeptide/kg treatments when assessed grossly. 4. The body weight of birds fed the 10 g casein phosphopeptide/kg diet or the 25-hydroxycholecalciferol diet was higher than birds fed the control diet. Although not significant, the body weight of birds fed the 14 g casein phosphopeptide/kg diet was also greater than the control birds. 5. The current experiment demonstrated that both casein phosphopeptide and 25-hydroxycholecalciferol can reduce the incidence of TD in the young broiler chicken. More research is required to explain the unexpected increase in body weight described above.

Effects of an anticariogenic casein phosphopeptide on calcium diffusion in streptococcal model dental plaques.

Casein phosphopeptides (CPP) stabilize amorphous calcium phosphate (ACP) and may be used to localize ACP in dental plaque, maintaining a state of supersaturation with respect to tooth enamel, reducing demineralization and enhancing remineralization. The aim here was to investigate these effects by measuring the effect of CPP-ACP on calcium diffusion in plaque. Using Dibdin's effusion system, calcium diffusion was measured in streptococcal model plaques. This demonstrated that by providing a large number of possible binding sites for calcium, 0.1% CPP-ACP reduces the calcium diffusion coefficient by about 65% at pH 7 and 35% at pH 5. Hence, CPP-ACP binds well to plaque, providing a large calcium reservoir within the plaque and slowing diffusion of free calcium. This is likely to restrict mineral loss during a cariogenic episode and provide a potential source of calcium for subsequent remineralization. Overall, once in place, CPP-ACP will restrict the caries process.

Role of models in assessing new agents for caries prevention--non-fluoride systems.

While fluoride is an effective anti-caries agent, the search for more effective alternative therapies continues. A wide range of non-fluoride anti-caries agents has been postulated, and this paper reviews some of the pre-clinical models that have been utilized in their evaluation and some of the pitfalls that must be avoided. Using data on the potential anti-caries efficacy of phosphopeptides obtained from casein, the caution that must be applied in extrapolating laboratory data to predict clinical performance is discussed. Evaluation strategies that focus on only one potential mode of action (e.g., inhibition of demineralization) may overestimate the true clinical efficacy which may arise from a combination of two or more effects (e.g., inhibition of demineralization and stimulation of remineralization). Although laboratory and in situ data predict anti-caries efficacy for sodium trimetaphosphate in combination with fluoride, this was not found in three-year clinical trials. A possible reason for this, the lack of suitable calibration methods, is discussed. Finally, some comments on the appropriateness of laboratory evaluation strategies are made.