Oleracone F Alleviates Cognitive Impairment and Neuropathology in APPswe/PSEN1dE9 Mice by Reducing the Expression of Vascular Cell Adhesion Molecule and Leukocyte Adhesion to Brain Vascular Endothelial Cells.

Alzheimer's disease (AD) is the most common neurodegenerative disease and the blood-brain barrier dysfunction has been suggested as a key pathological feature of the disease. Our research group successfully established a synthetic protocol for oleracones, a novel series of flavonoids isolated from the plant extract of Portulaca oleracea L. (PO). PO extract was reported to have anti-inflammatory and antioxidant effects, enhancing cognitive function. Thus, we investigated the effects and mechanism of oleracones on cognition using AD model transgenic mice (Tg; APPswe/PSEN1dE9). Oleracone F treatment significantly improved memory dysfunction in Tg mice. Oleracone F decreased the number, burden, and immunoreactivity of amyloid plaques and amyloid precursor protein (APP) protein levels in the brains of Tg mice compared to wild-type mice. Oleracone F also alleviated inflammation observed in Tg mice brains. In vitro studies in human microvascular endothelial cells (HBMVECs) demonstrated that oleracones D, E, and F blocked the elevations in VCAM-1 protein induced by tumor necrosis factor-α (TNF-α), hindering leukocyte adhesion to HBMVECs. Taken together, our results suggest that oleracones ameliorated cognitive impairment by blocking TNF-α-induced increases in VCAM-1, thereby reducing leukocyte infiltration to the brain and modulating brain inflammation.

Effects of mobile networks and Covid-19 on mobile shopping sales in South Korea.

Covid-19 has driven us abruptly to a new world of contactless society. It also compelled us to use online shopping, especially mobile shopping in South Korea, where the dominant mode of wireless communication was already 4G services when Covid-19 broke out. This paper examines the different roles of mobile networks and the Covid-19 pandemic in transforming mobile shopping submarkets in South Korea by estimating the long-term and short-term effects of these two factors on mobile shopping sales. We used a cointegration and an error correction model to estimate long-term and short-term effects separately. This paper finds that Covid-19 was a major short-term factor affecting sales in mobile shopping submarkets, while mobile network subscribers were a key long-term driving factor of mobile shopping sales growth.

Differentiating mobile broadband policies across diffusion stages: A panel data analysis.

This paper finds that policy mixes for mobile broadband diffusion need to be differentiated depending on where a country is situated in three stages of mobile broadband diffusion because as a mobile broadband market grows, demand constraints hindering subscription of mobile broadband will also change. A total of 115 countries are clustered into three groups (Take-off, Fast-Diffusion, and Saturated), categorized by their diffusion rates and diffusion speeds over four years from 2013 to 2016. With pooled and fixed effect panel data models, this paper examines which variables out of 23 explanatory variables were effective in promoting mobile broadband adoption globally. Further, by interacting explanatory variables with two group dummies, this paper identifies differential slope (policy) effects of each explanatory variable on mobile broadband adoption. The paper concludes that, among the three groups, considerable gaps exist in the size of effective policy choice sets: six for Take-off, ten for Fast-diffusion, and thirteen for Saturated, suggesting that the countries in the Take-off stage have a very narrow degree of latitude for developing mobile broadband promotion strategies.

Telmisartan Inhibits TNFα-Induced Leukocyte Adhesion by Blocking ICAM-1 Expression in Astroglial Cells but Not in Endothelial Cells.

Telmisartan is an angiotensin-II receptor blocker and acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPARγ). Several studies have demonstrated that telmisartan ameliorates depression and memory dysfunction and reduces brain inflammation. We hypothesized that the beneficial effects of telmisartan on brain could be due to modulation of the blood-brain barrier (BBB) function. Here, we examined the effect of telmisartan on tumor necrosis factor alpha (TNF-α)-induced expression of intercellular adhesion molecule 1 (ICAM-1) which plays an important role in leukocyte transcytosis through the BBB. Telmisartan blocked TNF-α-induced ICAM-1 expression and leukocyte adhesion in U87MG human glioma cells but showed no effect on human brain microvascular endothelial cells. In U87MG cells, a PPAR antagonist, GW9662 did not block the effect of telmisartan on ICAM1 expression but rather potentiated. Moreover, GW9662 caused no change in TNF-α-induced ICAM-1 expression, suggesting no implication of PPARγ in the telmisartan effect. Further studies showed that telmisartan blocked TNF-α- induced activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factorkappa B (NF-κB). In contrast, inhibitors of JNK, ERK1/2 and NF-κB but not p38, blocked ICAM-1 expression induced by TNF-α. Thus, our findings suggest that the beneficial effect of telmisartan is likely due to the reduction of astrocytic ICAM1 expression and leukocytes adhesion to astrocytes, and that this response was mediated by the inhibition of JNK/ERK1/2/NF-κB activation and in the PPAR-independent manner. In conclusion, this study enhances our understanding of the mechanism by which telmisartan exerts the beneficial brain function.

Harnessing artificial intelligence (AI) to increase wellbeing for all: The case for a new technology diplomacy.

The field of artificial intelligence (AI) is experiencing a period of intense progress due to the consolidation of several key technological enablers. AI is already deployed widely and has a high impact on work and daily life activities. The continuation of this process will likely contribute to deep economic and social changes. To realise the tremendous benefits of AI while mitigating undesirable effects will require enlightened responses by many stakeholders. Varying national institutional, economic, political, and cultural conditions will influence how AI will affect convenience, efficiency, personalisation, privacy protection, and surveillance of citizens. Many expect that the winners of the AI development race will dominate the coming decades economically and geopolitically, potentially exacerbating tensions between countries. Moreover, nations are under pressure to protect their citizens and their interests-and even their own political stability-in the face of possible malicious or biased uses of AI. On the one hand, these different stressors and emphases in AI development and deployment among nations risk a fragmentation between world regions that threatens technology evolution and collaboration. On the other hand, some level of differentiation will likely enrich the global AI ecosystem in ways that stimulate innovation and introduce competitive checks and balances through the decentralisation of AI development. International cooperation, typically orchestrated by intergovernmental and non-governmental organisations, private sector initiatives, and by academic researchers, has improved common welfare and avoided undesirable outcomes in other technology areas. Because AI will most likely have more fundamental effects on our lives than other recent technologies, stronger forms of cooperation that address broader policy and governance challenges in addition to regulatory and technological issues may be needed. At a time of great challenges among nations, international policy coordination remains a necessary instrument to tackle the ethical, cultural, economic, and political repercussions of AI. We propose to advance the emerging concept of technology diplomacy to facilitate the global alignment of AI policy and governance and create a vibrant AI innovation system. We argue that the prevention of malicious uses of AI and the enhancement of human welfare create strong common interests across jurisdictions that require sustained efforts to develop better, mutually beneficial approaches. We hope that new technology diplomacy will facilitate the dialogues necessary to help all interested parties develop a shared understanding and coordinate efforts to utilise AI for the benefit of humanity, a task whose difficulty should not be underestimated.

Effects of Epigallocatechin Gallate, an Antibacterial Cross-linking Agent, on Proliferation and Differentiation of Human Dental Pulp Cells Cultured in Collagen Scaffolds.

INTRODUCTION: This study aimed to evaluate the efficacy of epigallocatechin gallate (EGCG), an antibacterial cross-linking agent, on the proliferation and differentiation of human dental pulp cells (hDPCs) cultured in hydrogel collagen scaffolds. METHODS: The odontogenic differentiation induced by EGCG was evaluated by alkaline phosphatase (ALP) activity and odontogenic-related gene expression using real-time polymerase chain reaction. The antibacterial effect of EGCG was investigated by a disc diffusion assay in comparison with glutaraldehyde. Proliferation was analyzed by cell number counting under both optical and confocal laser scanning microscopes. To assess the mechanical properties of collagen treated with EGCG, the setting time, surface roughness, and compressive strength were measured. RESULTS: EGCG itself did not up-regulate the odontogenic-related markers (P > .05) although ALP activity was slightly increased. The proliferation and differentiation of hDPCs cultured in collagen increased significantly in the presence of EGCG (P < .05). The antibacterial activity of EGCG was similar to that of glutaraldehyde. The setting time of collagen was significantly shortened when it was treated with EGCG (P < .05). The surface roughness and compressive strength of the cross-linked collagen were higher than those of collagen without EGCG (P < .05). CONCLUSIONS: Our results showed that EGCG, the antibacterial cross-linking agent, promoted the proliferation and differentiation of hDPCs cultured in collagen scaffolds. Furthermore, the enhanced mechanical properties of collagen scaffolds induced by EGCG may play important roles in cell behavior. Consequently, the application of EGCG to collagen scaffolds might be beneficial for regenerative endodontic therapy.

Early Bone Formation at a Femur Defect Using CGF and PRF Grafts in Adult Dogs: A Comparative Study.

PURPOSE: The purpose of this study was to compare the predictability of new bone formation using an autologous concentrated growth factor (CGF) graft alone and platelet graft alone. MATERIALS AND METHODS: Four bony defects of 8 mm were formed, and 3.7- × 10-mm implants were placed in the right femur. The platelet-rich fibrin (PRF), CGF, and synthetic bone were grafted to the bone defect area. Enzyme linked immunosorbent assay quantitative analysis and microscopic analysis of the fibrinogen structure were performed. RESULTS: At 4 weeks, the comparisons of each experimental group showed a significant difference between the CGF group and the synthetic bone graft group. When comparing the CGF and allograft material groups, the allograft group showed significantly more new bone formation. In the case of vascular endothelial growth factor, CGF had 1.5 times more than PRF. CGF showed a fibrinogen structure with a constant diameter. CONCLUSION: When applied to a clinical case, CGF is predicted to show better results than PRF.

Effects of epicatechin, a crosslinking agent, on human dental pulp cells cultured in collagen scaffolds.

OBJECTIVE: The purpose of this study was to investigate the biological effects of epicatechin (ECN), a crosslinking agent, on human dental pulp cells (hDPCs) cultured in collagen scaffolds. MATERIAL AND METHOD: To evaluate the effects of ECN on the proliferation of hDPCs, cell counting was performed using optical and fluorescent microscopy. Measurements of alkaline phosphatase (ALP) activity, alizarin red staining, and real-time polymerase chain reactions were performed to assess odontogenic differentiation. The compressive strength and setting time of collagen scaffolds containing ECN were measured. Differential scanning calorimetry was performed to analyze the thermal behavior of collagen in the presence of ECN. RESULTS: Epicatechin increased ALP activity, mineralized nodule formation, and the mRNA expression of dentin sialophosphoprotein (DSPP), a specific odontogenic-related marker. Furthermore, ECN upregulated the expression of DSPP in hDPCs cultured in collagen scaffolds. Epicatechin activated the extracellular signal-regulated kinase (ERK) and the treatment with an ERK inhibitor (U0126) blocked the expression of DSPP. The compressive strength was increased and the setting time was shortened in a dose-dependent manner. The number of cells cultured in the ECN-treated collagen scaffolds was significantly increased compared to the cells in the untreated control group. CONCLUSIONS: Our results revealed that ECN promoted the proliferation and differentiation of hDPCs. Furthermore, the differentiation was regulated by the ERK signaling pathway. Changes in mechanical properties are related to cell fate, including proliferation and differentiation. Therefore, our study suggests the ECN treatment might be desirable for dentin-pulp complex regeneration.

Effects of epicatechin, a crosslinking agent, on human dental pulp cells cultured in collagen scaffolds

ABSTRACT Objective The purpose of this study was to investigate the biological effects of epicatechin (ECN), a crosslinking agent, on human dental pulp cells (hDPCs) cultured in collagen scaffolds. Material and Method To evaluate the effects of ECN on the proliferation of hDPCs, cell counting was performed using optical and fluorescent microscopy. Measurements of alkaline phosphatase (ALP) activity, alizarin red staining, and real-time polymerase chain reactions were performed to assess odontogenic differentiation. The compressive strength and setting time of collagen scaffolds containing ECN were measured. Differential scanning calorimetry was performed to analyze the thermal behavior of collagen in the presence of ECN. Results Epicatechin increased ALP activity, mineralized nodule formation, and the mRNA expression of dentin sialophosphoprotein (DSPP), a specific odontogenic-related marker. Furthermore, ECN upregulated the expression of DSPP in hDPCs cultured in collagen scaffolds. Epicatechin activated the extracellular signal-regulated kinase (ERK) and the treatment with an ERK inhibitor (U0126) blocked the expression of DSPP. The compressive strength was increased and the setting time was shortened in a dose-dependent manner. The number of cells cultured in the ECN-treated collagen scaffolds was significantly increased compared to the cells in the untreated control group. Conclusions Our results revealed that ECN promoted the proliferation and differentiation of hDPCs. Furthermore, the differentiation was regulated by the ERK signaling pathway. Changes in mechanical properties are related to cell fate, including proliferation and differentiation. Therefore, our study suggests the ECN treatment might be desirable for dentin-pulp complex regeneration.

Physical properties and biocompatibility of an injectable calcium-silicate-based root canal sealer: in vitro and in vivo study.

BACKGROUND: The aim of this study was to investigate the physical properties and biological effects of an experimentally developed injectable premixed calcium-silicate root canal sealer (Endoseal) in comparison with mineral trioxide aggregate (MTA) and a resin-based sealer (AHplus). METHODS: The pH, solubility, dimensional change, flow, and radiopacity of the materials were evaluated. Biocompatibility was evaluated on the basis of cell morphology and a viability test using MC3T3-E1 cells. For evaluate inflammatory reaction, the tested sealers were implanted into dorsal subcutaneous connective tissue of Sprague Dawley rats. After 7 days, the implants with the surrounding tissue were retrieved, and histological evaluation was performed. RESULTS: Endoseal showed high alkalinity similar to that of MTA. The solubility of the tested materials was similar. The dimensional change and flow of Endoseal was significantly higher than that of other materials (P < 0.05). The radiopacity of Endoseal was lower than that of AHplus (P < 0.05). The biocompatibility was similar to those of MTA. Inflammatory reaction of Endoseal was similar with that of MTA, but lower than that of AHplus (P < 0.05). CONCLUSIONS: The present study indicates that Endoseal has favorable physical properties and biocompatibility. Therefore, we suggest that Endoseal has the potential to be used as a predictable root canal sealer.

Odontogenic effects of a fast-setting calcium-silicate cement containing zirconium oxide.

A fast-setting calcium-silicate cement (Endocem) was introduced in the field of dentistry for use in vital pulp therapy. Similar to mineral trioxide aggregate (MTA), it contains bismuth oxide to provide radiopacity. Recently, another product, EndocemZr, which contains zirconium oxide (ZrO2) as a radiopacifier, was developed by the same company. In this study, the biological/odontogenic effects of EndocemZr were investigated in human primary dental pulp cells (hpDPCs) in vitro and on capped rat teeth in vivo. The biocompatibility of EndocemZr was similar to that of ProRoot and Endocem on the basis of cell viability tests and cell morphological analysis. The mineralization nodule formation, expression of odontogenic-related markers, and reparative dentin formation of EndocemZr group was similar to those of other material groups. Our results suggest that EndocemZr has the potential to be used as an effective material for vital pulp therapy, similar to ProRoot and Endocem.

Genipin, a cross-linking agent, promotes odontogenic differentiation of human dental pulp cells.

INTRODUCTION: The aim of this study was to investigate the effects of genipin, a natural collagen cross-linking agent, on odontogenic differentiation of human dental pulp cells (hDPCs) because the mechanical properties of collagen allow it to serve as a scaffold for engineering of pulp-dentin complex. Furthermore, the role of extracellular signal-regulated kinase (ERK) was investigated as a mediator of the differentiation. METHODS: The odontogenic differentiation was analyzed by alkaline phosphatase activity, real time-polymerase chain reaction, Western blotting, and alizarin red S staining. The morphologic features of hDPCs cultured in genipin-treated collagen were evaluated by scanning electron microscopy. For the assessment of mechanical properties of collagen treated with genipin, the surface roughness and compressive strength were measured. RESULTS: Alkaline phosphatase activity, the expression of odontogenic markers, and mineralized nodule formation increased in the genipin-treated group. Genipin also activated ERK, and treatment with ERK inhibitor blocked the expression of the markers. The cells cultured in genipin-treated collagen spread across the substrate and attached in close proximity to one another. The proliferation and differentiation of hDPCs cultured in genipin-treated collagen were facilitated. The mechanical properties of collagen, such as surface roughness and compressive strength, were increased by treatment with genipin. CONCLUSIONS: Our results show that genipin promotes odontogenic differentiation of hDPCs via the ERK signaling pathway. Furthermore, the enhanced mechanical properties of the collagen scaffold induced by genipin may play important roles in cell fate. Consequently, the application of genipin might be a new strategy for dentin-pulp complex regeneration.

Physical properties and biological/odontogenic effects of an experimentally developed fast-setting α-tricalcium phosphate-based pulp capping material.

BACKGROUND: Recently, fast-setting α-tricalcium-phosphate (TCP) cement was developed for use in the pulp capping process. The aim of this study was to investigate the physical properties and biological effects of α-TCP cement in comparison with mineral trioxide aggregate (MTA). METHODS: We measured the setting time, pH values, compressive strength, and solubility of the two materials. We evaluated biocompatibility on the basis of cell morphology and a viability test using human dental pulp cells (hDPCs). Chemical composition of each material was analyzed by energy dispersive x-ray spectroscopic (EDS) analysis. The expression of odontogenic-related genes was evaluated by Western blotting and immunofluorescence. The calcified nodule formation was measured by Alizarin red staining. We performed the pulp capping procedure on rat teeth for histological investigation. The data were analyzed by an independent t-test for physical properties, one-way ANOVA for biological effects, and the Mann-Whitney U test for tertiary dentin formation. A P value of less than 0.05 was considered statistically significant for all tests. RESULTS: The setting time, pH values, and compressive strength of α-TCP was lower than that of MTA (P < 0.05); however, the solubility of α-TCP was higher than that of MTA (P < 0.05). The resultant cell viability observed with the two materials was similar (P > 0.05). Scanning electron microscopy (SEM) revealed that cells attached to both materials were flat and had cytoplasmic extensions. The expression of odontogenic-related markers and mineralized nodule formation were higher in the two experimental groups compared to the control group (P < 0.05). Continuous tertiary dentin was formed underneath the capping materials in all samples of the tested groups. CONCLUSIONS: Our study demonstrated that the α-TCP exhibited biocompatibility and odontogenicity comparable to MTA, whereas it had a quicker setting time.