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.     

Changes in the gaseous H2S barrier properties of damaged silicate coated nylon 6 films

The damage imposed on SiO _x deposited nylon 6 films as a result of abrasion with a cotton cloth and Gelboflex testing was examined by evaluating the rate at which copper plates, which were enveloped by the damaged films, were corroded by H₂S. Abrasion with a cotton cloth caused some micro-cracking of the SiO _x layer and the permeation rate of H₂S approached that of the uncoated nylon 6 film. Damage to the SiO _x layer by twisting and crushing progressed gradually with the number of Gelboflex test cycles and correspondingly the corrosion rate of the copper plates increased. Comparison of the corrosion rates of the copper plates kept in the pouches made of various commercial films with those obtained for the damaged SiO _x deposited nylon 6 films showed a clear relationship between the H₂ permeation rate of the films and the corrosion rate of the copper plates by H₂S.     

A new method for power generation planning and problems of uncertainty

This paper presents a new method for power system planning which considers uncertainties of various system parameters as a part of the criterion function. The criterion function involves both the expected values of total system costs and the cost variances of different power plants. Previously, the authors proposed that these cost variances be evaluated from the existing power system plans in the form of the solutions to the inverse optimization problem, and then applied this procedure to the planning of power systems in Japan. However, because of the correlation between fuel and facility costs, the cost variances could not be determined as specific values. Here, to overcome this difficulty, the authors now introduce hydropower plants into the model as the so-called nonrisky elements and focus on the expenditure shares rather than the plant capacity shares. As a result, more reasonable results are obtained. This improved methodology is applied and the derived cost variances are shown. Further, using the resultant cost variances, the authors make Pareto-optimal power generation plans and demonstrate also the robustness of the method to price fluctuations.     

Autonomic nervous function of the patients with neurally mediated syncope

Although diagnosis of neurally mediated syncope (NMS) using head-up tilt (HUT) test has been established, the exact mechanism of NMS has not yet been elucidated. We evaluated beta and alpha-adrenergic function in NMS patients by pharmacological autonomic function test. The alpha-adrenergic sensitivity of NMS patients was significantly lower than that of control subjects. The patients who need low dose isoproterenol for provocation of syncope showed higher beta-adrenergic sensitivity than patients who developed syncope without isoproterenol. Thus, pharmacological autonomic function test was useful for evaluation of NMS patients.     

Nicotinamide Phosphoribosyltransferase as a Key Molecule of the Aging/Senescence Process

Aging is a phenomenon underlined by complex molecular and biochemical changes that occur over time. One of the metabolites that is gaining strong research interest is nicotinamide adenine dinucleotide, NAD⁺, whose cellular level has been shown to decrease with age in various tissues of model animals and humans. Administration of NAD⁺ precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), to supplement NAD⁺ production through the NAD⁺ salvage pathway has been demonstrated to slow down aging processes in mice. Therefore, NAD⁺ is a critical metabolite now understood to mitigate age-related tissue function decline and prevent age-related diseases in aging animals. In human clinical trials, administration of NAD⁺ precursors to the elderly is being used to address systemic age-associated physiological decline. Among NAD⁺ biosynthesis pathways in mammals, the NAD⁺ salvage pathway is the dominant pathway in most of tissues, and NAMPT is the rate limiting enzyme of this pathway. However, only a few activators of NAMPT, which are supposed to increase NAD⁺, have been developed so far. In this review, we will focus on the importance of NAD⁺ and the possible application of an activator of NAMPT to promote successive aging.     

Inhalational Anesthetics Inhibit Neuroglioma Cell Proliferation and Migration via miR-138, -210 and -335

Inhalational anesthetics was previously reported to suppress glioma cell malignancy but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNAs upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.