Search results for "OSTE"

Effect of total sonicated Aggregatibacter actinomycetemcomitans fragments on gingival stem/progenitor cells

2018

Background Aggregatibacter-actinomycetemcomitans (A.actinomycetemcomitans) are strongly associated with localized-aggressive-periodontitis (LAgP). The study’s aim was to test for the first time the effect of total sonicated A.actinomycetemcomitans-bacterial-fragments on gingival mesenchymal stem/progenitor cells’ (G-MSCs) proliferation and regenerative gene expression in-vitro. Material and Methods G-MSCs were isolated, characterized, expanded and stimulated by total sonicated A.actinomycetemcomitans-bacterial-fragments (0 (negative-control), 15, 60, 120 and 240µg/ml; serovar-b; n=6/group). Cellular proliferation and NF-κβ (NFKB1), Alkaline Phosphatase (ALPL), Collagen-I (COL1A1), Collagen-…

Phenolic Compounds in Extra Virgin Olive Oil Stimulate Human Osteoblastic Cell Proliferation.

2016

In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11-16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective…

Heat shock protein 70 dampens the inflammatory response of human PDL cells to mechanical loading in vitro

2019

BACKGROUND AND OBJECTIVE Previously, we demonstrated an inflammatory response of human PDL (hPDL) cells to mechanical loading. The cellular reaction was dampened by heat pre-treatment suggesting a protective role for heat shock proteins (HSP) during stress-induced ischemia. Here we explored if HSP70, which has already been documented in the pressure zone of tooth movement, might be regulatorily involved in the attenuation of the inflammatory response. MATERIALS AND METHODS Fifth passage hPDL cells were mechanically loaded in the presence of the HSP70 inhibitor VER155008. Cell morphology, HSP70 expression, viability, IL-6 and IL-8 expression were determined by means of microscopy, realtime-P…

AB052. P-20. Phase 2, open-label study of second-line M7824 treatment in patients with locally advanced or metastatic biliary tract cancer

2019

BACKGROUND: Transforming growth factor β (TGF-β) signaling promotes tumor immunosuppression; its inhibition in the tumor microenvironment may enhance the response to anti-PD-L1 treatment. M7824 is an innovative first-in-class bifunctional fusion protein composed of 2 extracellular domains of TGF-βRII (a TGF-β “trap”) fused to a human IgG1 mAb against PD-L1. Building upon encouraging efficacy observed in a phase 1 study, the present study will evaluate M7824 clinical benefit in patients with pretreated biliary tract cancer (BTC). METHODS: This multicenter, international trial is evaluating M7824 monotherapy in patients with locally advanced or metastatic (LA/M) BTC unselected for tumor PD-L1…

2019

Golgi α-mannosidase II (GMII) is a glycoside hydrolase playing a crucial role in the N-glycosylation pathway. In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis. GMII therefore is a possible molecular target for anticancer agents. Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.

Impact of Lipid Components and Emulsifiers on Plant Sterols Bioaccessibility from Milk-Based Fruit Beverages.

2016

Sterol bioaccessibility (BA) of three plant sterol (PS)-enriched milk-based fruit beverages (MFb) with different fat contents (1.1–2.4%), lipid sources (animal or vegetable), and without or with emulsifiers (whey proteins enriched with milk fat globule membrane (MFGM) or soy lecithin) was evaluated after simulated gastrointestinal digestion. The BA of total PS followed the order 31.4% (MFbM containing milk fat and whey proteins enriched with MFGM) = 28.2% (MFbO containing extra virgin olive oil and soy lecithin) > 8.7% (MFb without fat addition). Total and individual PS content in the bioaccessible fractions followed the order MFbM > MFbO > MFb. Consequently, formulation with MFGM is propos…

Changes in Serine Racemase-Dependent Modulation of NMDA Receptor: Impact on Physiological and Pathological Brain Aging

2018

International audience; The N-methyl-D-Aspartate glutamate receptors (NMDARs) are pivotal for the functional and morphological plasticity that are required in neuronal networks for efficient brain activities and notably for cognitive-related abilities. Because NMDARs are heterogeneous in subunit composition and associated with multiple functional regulatory sites, their efficacy is under the tonic influence of numerous allosteric modulations, whose dysfunction generally represents the first step generating pathological states. Among the enzymatic candidates, serine racemase (SR) has recently gathered an increasing interest considering that it tightly regulates the production of D-serine, an…

Entrapment and characterization of functional allosteric conformers of hemocyanin in sol–gel matrices

2016

Hemocyanins are giant oxygen transport proteins of molluscs and arthropods, which display high cooperativity and a complex pattern of conformations, generated by hierarchical allosteric interactions of their complex quaternary structure. A still unanswered question is the correlation between the functional properties of the postulated conformers and structural features that govern their oxygen binding, such as metal complex coordination. In this study we focus on the dodecameric hemocyanin of the crustacean Carcinus aestuarii, with the aim to obtain a functional and structural characterization of the individual conformational states giving rise to cooperativity, by entrapping hemocyanin int…

SNPs in bone-related miRNAs are associated with the osteoporotic phenotype

2017

AbstractBiogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we…

Neuroactive Steroids Reverse Tonic Inhibitory Deficits in Fragile X Syndrome Mouse Model

2018

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. A reduction in neuronal inhibition mediated by γ-aminobutyric acid type A receptors (GABAARs) has been implicated in the pathophysiology of FXS. Neuroactive steroids (NASs) are known allosteric modulators of GABAAR channel function, but recent studies from our laboratory have revealed that NASs also exert persistent metabotropic effects on the efficacy of tonic inhibition by increasing the protein kinase C (PKC)-mediated phosphorylation of the α4 and β3 subunits which increase the membrane expression and boosts tonic inhibition. We have assessed the GABAergic signaling in the hippocampus of fragile X ment…