Efficacy and Blood Levels of Lacosamide in Patients with Focal Epilepsy.

: The aim of this paper is to analyze clinical targets for lacosamide (LCM) blood levels in patients with focal epilepsy. Referring to the LCM optimal range will encourage us to think about the importance and usefulness of measuring its blood levels. : A total of 101 (45 female, 56 male) patients were treated with LCM.

Osteoprotegerin secretion and its inhibition by RANKL in osteoblastic cells visualized using bioluminescence imaging.

Bone remodeling is regulated by the interaction between receptor activator of nuclear factor kappa-B ligand (RANKL) and its receptor RANK on osteoblasts and osteoclasts, respectively. Osteoprotegerin (OPG) is secreted from osteoblasts and inhibits osteoclast differentiation by acting as a decoy receptor for RANKL. Despite its importance, the mechanism underlying the secretion of OPG remains poorly understood.

Wnt family members regulating osteogenesis and their origins.

Wnt signaling plays an important role in the regulation of bone metabolism. Wnt activates the β-catenin-mediated canonical pathway and β-catenin-independent non-canonical pathway. When Wnt ligands bind to the co-receptors low density lipoprotein receptor-related protein (Lrp)5 or Lrp6, and a seven-transmembrane receptor frizzled, the canonical pathway is activated.

The G9a histone methyltransferase represses osteoclastogenesis and bone resorption by regulating NFATc1 function.

Epigenetic modifications affect cell differentiation via transcriptional regulation. G9a/EHMT2 is an important epigenetic modifier that catalyzes the methylation of histone 3 lysine 9 (H3K9) and interacts with various nuclear proteins. In this study, we investigated the role of G9a in osteoclast differentiation.

Differential osteoblastic activity in primary metaphyseal trabecular and secondary trabeculae of c-fos deficient mice.

Objectives: It has been highlighted that osteoblastic activities in remodeling-based bone formation are coupled with osteoclastic bone resorption while those in modeling-based bone formation are independent of osteoclasts. This study aimed to verify whether modeling-based bone formation can occur in the absence of osteoclasts.

Methods: We performed histochemical analyses on the bone of eight-week-old male wild-type and c-fos mice.

The vitamin D receptor in osteoblastic cells but not secreted parathyroid hormone is crucial for soft tissue calcification induced by the proresorptive activity of 1,25(OH)D.

The vitamin D receptor (VDR) is expressed most abundantly in osteoblasts and osteocytes (osteoblastic cells) in bone tissues and regulates bone resorption and calcium (Ca) and phosphate (P) homeostasis in association with parathyroid hormone (PTH). We previously reported that near-physiological doses of vitamin D compounds suppressed bone resorption through VDR in osteoblastic cells. We also found that supra-physiological doses of 1α,25-dihydroxyvitamin D [1,25(OH)D] induced bone resorption and hypercalcemia via VDR in osteoblastic cells.

Sclerostin deficiency effectively promotes bone morphogenetic protein-2-induced ectopic bone formation.

Background And Objective: Severe periodontitis causes alveolar bone resorption, resulting in tooth loss. Developments of tissue regeneration therapy that can restore alveolar bone mass are desired for periodontal disease. The application of bone morphogenetic protein-2 (BMP-2) has been attempted for bone fractures and severe alveolar bone loss.

Effects of Irradiation by Carbon Dioxide Laser Equipped With a Water Spray Function on Bone Formation in Rat Tibiae.

Background/aim: Irradiation of tissue with carbon dioxide (CO) laser shows a characteristic thermal effect that causes vaporization of tissue in the target region. However, the thermal effect in places other than the target region induces tissue damage. Two methods are used: high reactive-level laser therapy (HLLT), aimed at surgical treatment, and low reactive-level laser therapy (LLLT), aimed at cell and tissue activation.

p57Kip2 is an essential regulator of vitamin D receptor-dependent mechanisms.

A cyclin-dependent kinase (CDK) inhibitor, p57Kip2, is an important molecule involved in bone development; p57Kip2-deficient (p57-/-) mice display neonatal lethality resulting from abnormal bone formation and cleft palate. The modulator 1α,25-dihydroxyvitamin D3 (l,25-(OH)2VD3) has shown the potential to suppress the proliferation and induce the differentiation of normal and tumor cells. The current study assessed the role of p57Kip2 in the 1,25-(OH)2VD3-regulated differentiation of osteoblasts because p57Kip2 is associated with the vitamin D receptor (VDR).

Mesenchymal cell TRPM7 expression is required for bone formation via the regulation of chondrogenesis.

Transient receptor potential melastatin-subfamily member 7 (TRPM7) is a bifunctional protein containing a kinase fused to an ion channel permeated with cations, including Ca and Mg. Trpm7-null mice show embryonic lethality. Paired related homeobox 1 (Prx1) is expressed in undifferentiated mesenchymal cells such as the progenitor cells of both chondrocytes and osteoblasts involved in limb skeleton formation.

Association between Type 2 Diabetes and Classification of Periodontal Disease Severity in Japanese Men and Women: A Cross-Sectional Study.

Background: to evaluate the association between type 2 diabetes and periodontal disease severity using the rate of alveolar bone loss (ABL) and high-sensitivity C-reactive protein (hs-CRP) value as indices.

Methods: In this cross-sectional study of 372 patients (mean age ± SD, 53.2 ± 11.

Positive and Negative Regulators of Sclerostin Expression.

Sclerostin is secreted from osteocytes, binds to the Wnt co-receptor Lrp5/6, and affects the interaction between Wnt ligands and Lrp5/6, which inhibits Wnt/β-catenin signals and suppresses bone formation. Sclerostin plays an important role in the preservation of bone mass by functioning as a negative regulator of bone formation. A sclerostin deficiency causes sclerosteosis, which is characterized by an excess bone mass with enhanced bone formation in humans and mice.

Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin-Deficient Mice.

Background The biological mechanism of action for osteoprotegerin, a soluble decoy receptor for the receptor activator of nuclear factor-kappa B ligand in the vascular structure, has not been elucidated. The study aim was to determine if osteoprotegerin affects aortic structural integrity in angiotensin II (Ang II)-induced hypertension. Methods and Results Mortality was higher (<0.

Evidence for the major contribution of remodeling-based bone formation in sclerostin-deficient mice.

Bone formation by osteoblasts is achieved through remodeling-based bone formation (RBBF) and modeling-based bone formation (MBBF). The former is when bone formation occurs after osteoclastic bone resorption to maintain bone mass and calcium homeostasis. The latter is when new bone matrices are added on the quiescent bone surfaces.

Photobase-Triggered Formation of 3D Epitaxially Fused Quantum Dot Superlattices with High Uniformity and Low Bulk Defect Densities.

Highly ordered epitaxially fused colloidal quantum dot (QD) superlattices (epi-SLs) promise to combine the size-tunable photophysics of QDs with the efficient charge transport of bulk semiconductors. However, current epi-SL fabrication methods are crude and result in structurally and chemically inhomogeneous samples with high concentrations of extended defects that localize carriers and prevent the emergence of electronic mini-bands. Needed fabrication improvements are hampered by inadequate understanding of the ligand chemistry that causes epi-SL conversion from the unfused parent SL.

Inhibitor of protein kinase N3 suppresses excessive bone resorption in ovariectomized mice.

Introduction: The long-term inhibition of bone resorption suppresses new bone formation because these processes are coupled during physiological bone remodeling. The development of anti-bone-resorbing agents that do not suppress bone formation is urgently needed. We previously demonstrated that Wnt5a-Ror2 signaling in mature osteoclasts promoted bone-resorbing activity through protein kinase N3 (Pkn3).

Characterization, pharmacokinetics, and pharmacodynamics of anti-Siglec-15 antibody and its potency for treating osteoporosis and as follow-up treatment after parathyroid hormone use.

Recent studies have established the idea that Siglec-15 is involved in osteoclast differentiation and/or function, and it is anticipated that therapies suppressing Siglec-15 function can be used to treat bone diseases such as osteoporosis. We have produced rat monoclonal anti-Siglec-15 antibody (32A1) and successively generated humanized monoclonal anti-Siglec-15 antibody (DS-1501a) from 32A1. Studies on the biological properties of DS-1501a showed its specific binding affinity to Siglec-15 and strong activity to inhibit osteoclastogenesis.

Ultrafast vibrational dynamics of the tyrosine ring mode and its application to enkephalin insertion into phospholipid membranes as probed by two-dimensional infrared spectroscopy.

Enkephalins are small opioid peptides whose binding conformations are catalyzed by phospholipid membranes. Binding to opioid receptors is determined by the orientation of tyrosine and phenylalanine side chains. In this work, we investigate the effects of different charged phospholipid headgroups on the insertion of the tyrosine side chain into a lipid bilayer using a combination of 2D IR spectroscopy, anharmonic DFT calculations, and third order response function modeling.

Odontoblast death drives cell-rich zone-derived dental tissue regeneration.

Severe dental tissue damage induces odontoblast death, after which dental pulp stem and progenitor cells (DPSCs) differentiate into odontoblast-like cells, contributing to reparative dentin. However, the damage-induced mechanism that triggers this regeneration process is still not clear. We aimed to understand the effect of odontoblast death without hard tissue damage on dental regeneration.

RANKL/OPG ratio regulates odontoclastogenesis in damaged dental pulp.

Bone-resorbing osteoclasts are regulated by the relative ratio of the differentiation factor, receptor activator NF-kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Dental tissue-localized-resorbing cells called odontoclasts have regulatory factors considered as identical to those of osteoclasts; however, it is still unclear whether the RANKL/OPG ratio is a key factor for odontoclast regulation in dental pulp. Here, we showed that odontoclast regulators, macrophage colony-stimulating factor-1, RANKL, and OPG were detectable in mouse pulp of molars, but OPG was dominantly expressed.

Osteoclast differentiation by RANKL and OPG signaling pathways.

Introduction: In bone tissue, bone resorption by osteoclasts and bone formation by osteoblasts are repeated continuously. Osteoclasts are multinucleated cells that derive from monocyte-/macrophage-lineage cells and resorb bone. In contrast, osteoblasts mediate osteoclastogenesis by expressing receptor activator of nuclear factor-kappa B ligand (RANKL), which is expressed as a membrane-associated cytokine.

The Vitamin D Receptor in Osteoblast-Lineage Cells Is Essential for the Proresorptive Activity of 1α,25(OH)2D3 In Vivo.

We previously reported that daily administration of a pharmacological dose of eldecalcitol, an analog of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], increased bone mass by suppressing bone resorption. These antiresorptive effects were found to be mediated by the vitamin D receptor (VDR) in osteoblast-lineage cells. Using osteoblast-lineage-specific VDR conditional knockout (Ob-VDR-cKO) mice, we examined whether proresorptive activity induced by the high-dose 1α,25(OH)2D3 was also mediated by VDR in osteoblast-lineage cells.

Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction.

Microglia are the principal phagocytes that clear cell debris in the central nervous system (CNS). This raises the question, which cells remove cell debris when microglial phagocytic activity is impaired. We addressed this question using Siglech mice, which enable highly specific ablation of microglia.