Host-modulating therapeutic approaches in periodontal disease: histological evaluations

Periodontal disease is an oral inflammatory disease often associated with damage to the soft tissues and hard structures that support teeth. Within the subgingival biofilm, multiple microorganisms initiate inflammatory responses that can lead to a chronic oral inflammatory state, in which periodontal ligament may be damaged leading to alveolar bone loss. In recent studies, amnion-derived cellular cytokine solution (ACCS) and cytokines secreted by the amnion-derived multipotent progenitor cells (AMPs) obtained from the placenta illustrated evidence of wound healing, promotion of macrophage activity, and infected tissue repair. Furthermore, ACCS were capable of preventing periodontal inflammation induced by Porphyromonas gingivalis (P. gingivalis) in an experimental model, suggesting its role in modulating host's inflammatory response in order to arrest, if not eradicate, inflammation in periodontal tissues.. This study aimed to investigate a novel combination of ACCS that specifically targeted the bone tissues. Whereas in previous study, ACCS was tested to identify the efficacy of its ability to reduce inflammation and to repair damages in gingiva and reduce alveolar bone loss, ACCS-B was tested here to determine its impact on bone turnover. The study used a periodontal model of rabbit jaws to induce periodontitis. Periodontitis-specific pathogen P. gingivalis was applied in a carboxymethyl cellulose (CMC) slurry topically applied to the mandibular second premolars at the site of silk ligatures.. The silk ligatures were placed to serve as the retention for the P. gingivalis slurry. The protocol followed two phases, the disease induction phase (6 weeks) and the treatment phase (6 weeks). In the disease induction phase, 24 New-Zealand White rabbits were induced with topical P. gingivalis every other day on the mandibular premolars. At the end of this phase, 3 rabbits were randomly selected and sacrificed to serve as the baseline disease group. Of the remaining 21 rabbits, 3 rabbits were kept untreated and served as untreated-control group and the remaining 18 rabbits were randomly assigned to 3 different treatment groups: Placebo Treatment (Saline), ACCS-U treatment, and ACCS-B treatment. During the treatment phase, each treatment group received its respective treatments to the ligated sites 3 times a week in an every-other-day fashion. After 6 weeks, the rabbit jaws were evaluated histologically. At the end of treatment phase, the untreated group exhibited significant progression of periodontal disease evident by the destruction of soft and hard tissue on the site of interest. ACCS-U and ACCS-B showed substantial reduction of tissue inflammation and crestal bone loss compared to those in baseline disease, untreated, and saline-treated groups, however there were no statistically significant differences between ACCS-B and ACCS-Utreated sites. . Histological findings, specifically Masson's Trichrome stained sections, revealed that collagen deposition and new bone formations were actively present in the alveolar bone of ACCS-treated groups. Moreover, quantitative assessments of inflammatory cell activity and osteoclastic activity at the crestal and along the bone surfaces of the ligated sites by Hematoxylin-Eosin stains and tartrate-resistant acid phosphatase stains respectively, confirmed the anti-inflammatory activity by the ACCS-treatments. The osteocalcin stained cells also revealed the initiation of bone formation and bone repair in the ACCS-treated groups. These results state a clear indication of control of inflammatory disease and as a result, bone formation and tissue repair in both ACC-U and ACC-B treated groups.. As for the untreated group and the baseline disease group, significant disease progression is highlighted by bone loss and high level of inflammation in the site of interest. Although ACCS-B was inferior to previously tested ACCS-U with regard to anti-inflammatory effects and bone formation it clearly demonstrated its future use as potential treatment for periodontal disease, along with restoration of damaged tissues. These results further solidify findings that ACCS acts through host-modulated anti-inflammatory actions in the inflammatory conditions

Diagnostic approaches for neurodevelopmental disorders using human-derived olfactory epithelial cells

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2 '-5 ' oligoadenylate synthetase-like 1 (OASL1) protects against atherosclerosis by maintaining endothelial nitric oxide synthase mRNA stability

Maintaining optimal eNOS levels is important during cardiovascular events, although little is known regarding the mechanism of eNOS protection. Here, the authors show a regulatory role of endothelial OASL1 in maintaining eNOS mRNA stability and vascular biology under atheroprone conditions. Endothelial nitric oxide synthase (eNOS) decreases following inflammatory stimulation. As a master regulator of endothelial homeostasis, maintaining optimal eNOS levels is important during cardiovascular events. However, little is known regarding the mechanism of eNOS protection. In this study, we demonstrate a regulatory role for endothelial expression of 2 '-5 ' oligoadenylate synthetase-like 1 (OASL1) in maintaining eNOS mRNA stability during athero-prone conditions and consider its clinical implications. A lack of endothelial Oasl1 accelerated plaque progression, which was preceded by endothelial dysfunction, elevated vascular inflammation, and decreased NO bioavailability following impaired eNOS expression. Mechanistically, knockdown of PI3K/Akt signaling-dependent OASL expression increased Erk1/2 and NF-kappa B activation and decreased NOS3 (gene name for eNOS) mRNA expression through upregulation of the negative regulatory, miR-584, whereas a miR-584 inhibitor rescued the effects of OASL knockdown. These results suggest that OASL1/OASL regulates endothelial biology by protecting NOS3 mRNA and targeting miR-584 represents a rational therapeutic strategy for eNOS maintenance in vascular disease

Development of plasma sources and diagnostics for the simulation of fusion edge plasmas

© 2022, The Korean Physical Society.Although the research on divertors and scrape-off layers (SOLs) has been not as focused on as the recent success of the Korean fusion program, a few linear plasma devices have been developed for simulating divertor and SOL plasmas: (1) diversified plasma simulator (DiPS), a versatile linear machine, has been developed for simulations of divertor and space plasmas with various electric probes, such as single, triple, and Mach Probes and gridded energy analyzer. DiPS consists of two major parts: a divertor plasma simulator with a LaB 6 DC plasma source and a space plasma simulator with a helicon RF plasma source, (2) divertor plasma simulator-1 (DiPS-1) is a part of DiPS with only a LaB 6 cathode, where a low-power laser-induced fluorescence (LIF) is added and more electric probe diagnostics are augmented; it is dedicated only for fusion edge and divertor plasmas, (3) Divertor Plasma Simulator-2 (DiPS-2) has been modified from the DiPS-1 by adding a magnetic nozzle with a limiter structure and by removing the helicon source and space chamber. DiPS-2 is a linear plasma device with a 4-inch LaB 6 cathode, the same as DiPS-1, and it is focused on the development of various diagnostics, such as those used for LIF and laser Thomson scattering (LTS) along with various electric probes, on the divertor and scrape-off plasmas and on the plasma-material interaction (PMI) research, such as that of tungsten and graphite as plasma-facing components (PFCs), (4) A Multi-Purpose Plasma (MP 2) device is a renovation of the Hanbit mirror device [Kwon et al., Nucl. Fusion 43, 686 (2003)] with the installation of two plasma sources: LaB 6 (DC) and helicon (RF) plasma sources. A honeycomb-like large-area LaB 6 (HLA-LaB 6) cathode has been developed for the divertor plasma simulation to improve the resistance against the thermal shock fragility for large (8-inch) and high density plasma generation, (5) DiPS-2 has been augmented by adding another cylindrical device, called the Dust interaction with Surfaces Chamber (DiSC) for the generation and diagnostics of dusts. This combined system (DiPS-2+DiSC) has added two more diagnostics: Laser Photo-Detachment (LPD) for dust density and laser Mie Scattering (LMS) for dust size. Moreover, dusts or negative ions have been analyzed by using electric probes and capacitive diagram gauges in Transport and Removal of Dusts (TReD) device.N

Simulations of fusion edge plasmas by linear plasma devices: physics and plasma–material interactions

© 2022, The Korean Physical Society.Because a fusion edge plasma contains various atomic and molecular processes, along with various plasma–material interactions (PMIs) for post-mortem analyses, a linear plasma device can simulate divertor and scrape-off layer (SOL) plasmas with DC edge relevant parameters, although it cannot generate a high ion temperature and toroidicity with much less power density compared to toroidal devices. The Divertor Plasma Simulator-2 (DiPS-2), a linear device with an LaB6 DC cathode, has been used for a few fusion-relevant physics experiments, including edge localized mode (ELM) simulation and edge transport of diffusion and convection. An ELM simulation has been performed by modulating the magnetic field relevant to the pressure modulation of a toroidal device, and the diffusion coefficients of free and bound presheaths have been measured in simulations of divertor or limiter transport. Moreover, the convection of the filament or the bubble expansion to the first wall has also been analyzed. In addition to various atomic and molecular processes in SOL and divertor plasmas, PMIs must be analyzed both on and beneath the surface of the plasma-facing components (PFCs) because of surface modification. Using DiPS-2 and other linear devices along with Korea Superconducting Tokamak Advanced Research (KSTAR), PMIs have been analyzed in terms of the following elements or processes: (1) boronizations, both for dust interactions with the surface chamber (DiSC) and KSTAR device, are analyzed; (2) carbon damage by the dense heat flux of DiPS-2 is experimentally investigated; (3) the density profile of the lithium injection gettering of hydrogen and its transport experiments (LIGHT-1) device is analytically calculated; (4) the effect of nitrogen on the relaxation of the heat flux to the divertor tile is experimentally analyzed; and (5) tungsten as the divertor tile material is analyzed via laser ELM simulations in terms of dust generation and surface modification.N