Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.     

Combustion synthesis of AlN doped with carbon and oxygen

Carbon-and-oxygen-doped AlN specimens were prepared by combustion synthesis using Al, graphite, and AlN. Graphite addition changed the product color from white to blue. By XRD, the lattice constant increased slightly with increasing carbon content. Blue AlN powder was synthesized with a molar ratio of the diluent AlN of 0.2-0.5 with a fixed graphite content of 0.05. At an AlN molar ratio exceeding 0.6, carbon was not successfully incorporated due to the lower reaction temperature. Calcination at 800°C in air removed residual graphite without changing the crystal structure or product color. Oxygen, nitrogen, and carbon analyses revealed that blue AlN powders contained 0.45-0.54 mass% carbon and 1.4-1.6 mass% oxygen, while the undoped AlN contained 0.021 mass% carbon and 0.94 mass% oxygen. The origin of the white-to-blue color change was investigated via reflection measurements. Blue AlN exhibits an absorption peak at 634 nm (1.96 eV). From first-principles electronic structure calculations, the C-doped AlN and carbon-and-oxygen-doped AlN with a 1:1 ratio could be classified as p-type, whereas the O-doped AlN and 1:3 carbon-and-oxygen-doped AlN were n-type. One reason for the absorption peak at 634 nm may be a transition from the conduction band to an upper unoccupied state. These results suggest the possible control of optical and electronic properties of AlN via carbon-and-oxygen doping.     

Multifunctional Hydrophobized Microparticles for Accelerated Wound Healing after Endoscopic Submucosal Dissection

Endoscopic submucosal dissection (ESD) provides strong therapeutic benefits for early gastrointestinal cancer as a minimally invasive treatment. However, there is currently no reliable treatment to prevent scar contracture resulting from ESD which may lead to cicatricial stricture. Herein, a multifunctional colloidal wound dressing to promote tissue regeneration after ESD is demonstrated. This sprayable wound dressing, composed of hydrophobized microparticles, exhibits the multifunctionality necessary for wound healing including tissue adhesiveness, blood coagulation, re‐epithelialization, angiogenesis, and controlled inflammation based on hydrophobic interaction with biological systems. An in vivo feasibility study using swine gastric ESD models reveals that this colloidal wound dressing suppresses fibrosis and accelerates wound healing. Multifunctional colloidal and sprayable wound dressings have an enormous therapeutic potential for use in a wide range of biomedical applications including accelerated wound healing after ESD, prevention of perforation, and the treatment of inflammatory diseases.     

Study of the Antioxidative Properties of Several Amino Acid-Type Surfactants and their Synergistic Effect in Mixed Micelle

Cysteine and methionine, two sulfur-containing amino acids (AA), were introduced in their surfactant forms as potential antioxidants. The antioxidative (AOX) properties of lauroyl methionine (C12-Met) and lauroyl cysteine (C12-Cys) was investigated by means of the oxygen radical absorbance capacity assay. Both the surfactants exhibited excellent AOX behavior at the premicellar state and micellar medium. The AOX behavior was found to be comparable for both the surfactants at their premicellar states. However, in micellar medium, C12-Met showed better AOX property than C12-Cys. The AOX power of the surfactants was compared with other previously developed AA-type surfactants. The order of the AOX power was found to be: C12-tryptophan > C12-tyrosine ≈ C12-methionine ≈ C12-cysteine > C12-histidine at the premicellar state and C12-tryptophan > C12-tyrosine > C12-methionine > C12-cysteine > C12-histidine at the micellar state. C12-Cys displayed lower AOX property in micellar medium due to its dimer formation tendency. Based on the HPLC and UPLC-Q-TOF-MS analysis, the dimer formation of C12-Cys was found to be accelerated due to the micellar environment and results into negative synergistic effect on other aromatic AA-type surfactants. However, the presence of C12-His in the micellar solution of C12-Cys resulted no synergistic effect due to stronger H-bonding between the surfactants and resulting less dimer formation.     

Graded evolution of anisotropic microstructure during sintering from crystal-oriented powder compact

Anisotropic sintering, including shrinkage and grain growth, was examined for c-axis-oriented (Sr,Ca)₂NaNb₅O₁₅ (SCNN) ceramics, which were prepared by colloidal processing under a magnetic field. In the c-axis-oriented SCNN powder compact, shrinkage and grain growth along the c-axis were higher than those along the a-axis. The anisotropic microstructural development was clearly associated with anisotropic sintering shrinkage. X-ray diffraction, scanning electron microscopy, and energy back scattering diffraction showed that the grain growth of oriented particles by including random grains contribute to the development of the oriented microstructure. Finally, the highly crystal-oriented SCNN ceramics with a densified microstructure were obtained through anisotropic sintering. These results clearly showed the potential to develop a well-defined anisotropic microstructure during sintering by designing and controlling the particle packing structure in a powder compact.     

Propagation and termination of an internal crack in continuously cast austenitic stainless steel analyzed by ∑ values and the Schmid factor

The formation mechanism of an internal crack was clarified from the viewpoint of the crystallography and thermal expansion. An inverse pole figure map obtained by EBSD pattern showed that the crack propagated along the grain boundaries having high ∑ values within the columnar zone. After the crack initiation, these positions were considered to undergo cracking followed by propagation toward the equiaxed side. Near the termination position, the grains ahead of crack propagation had a Schmid factor higher than 0.45 consuming elastic strain energy. Thermal expansion measurements showed that the grain with (0 0 1) orientation had the largest expansion while that with (0 1 1) the smallest. The grain boundaries neighboring the combination of (0 0 1) and (0 1 1) grains had the largest thermal stress. Therefore, thermal stress contributed to the initiation of cracking. It was thus proposed to enlarge the equiaxed zone to prevent cracking by discontinuing the crack propagation.     

Engineering of Lipid Nanoparticles by the Multifunctionalization of the Surface with Amino Acid Derivatives for the Neutralization of a Target Toxic Peptide

Protein affinity reagents (e.g., antibodies) are often used for basic research, diagnostics, separations, and disease therapy. Although a lot of “synthetic” protein affinity reagents have been developed as a cost-effective alternative to antibodies, their low biocompatibility is a considerable problem for clinical application. Lipid nanoparticles (LNP) represent a highly biocompatible drug delivery agent. However, little has been reported that LNP itself works as a protein affinity reagent in living animals. Here, LNP is engineered for binding to and neutralizing a target toxic peptide in living animals by multifunctionalization with amino acid derivatives. Multifunctionalized LNP (MF-LNP) is prepared using amino acid derivative-conjugated lipids. Optimized MF-LNP exhibits nanomolar affinity to the target toxic peptide and inhibits toxic peptide-dependent hemolysis and cytotoxicity. In addition, MF-LNP captures and neutralizes the toxic peptide after intravenous injection in the bloodstream; in addition, MF-LNP does not release the toxic peptide in the accumulated organ. These results reveal the potential of using LNP as a highly biocompatible protein affinity reagent such as an antidote.     

Frequency of Upward Lightning Hits to Wind Turbines in Winter

In recent years, frequent damage to wind turbines by winter lightning has been reported in the region along the Sea of Japan. It is a serious finding that lightning hits concentrate on wind turbines in this region. The authors investigated the increase rate of the frequency of lightning hits on wind turbines due to wind turbine construction by using LLS (lightning location system) data. As a result, an experimental formula to estimate the increase rate of the frequency of lightning hits on wind turbines as a function of parameters related to the construction conditions, namely the height of wind turbines, the height above sea level, and the latitude, is proposed.