• Journal of Veterinary Science
• /
• v.23 no.4
• /
• pp.56.1-56.17
• /
• 2022

Background: At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms remain ambiguous. Objectives: This paper was designed to probe the toxicity of DFS exposure on the hepatic proteome of broiler chickens. Methods: Twenty 30-day-old broiler chickens were randomized evenly into two groups (n = 10). DFS was administered orally at 10mg/kg body weight in group A, while the chickens in group B were perfused with saline as a control. Histopathological observations, serum biochemical examinations, and quantitative real-time polymerase chain reaction were performed to assess the liver injury induced by DFS. Proteomics analysis of the liver samples was conducted using isobaric tags for relative and absolute quantification (iTRAQ) technology. Results: Ultimately, 201 differentially expressed proteins (DEPs) were obtained, of which 47 were up regulated, and 154 were down regulated. The Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to screen target DEPs associated with DFS hepatotoxicity. The regulatory relationships between DEPs and signaling pathways were embodied via a protein-protein interaction network. The results showed that the DEPs enriched in multiple pathways, which might be related to the hepatotoxicity of DFS, were "protein processing in endoplasmic reticulum," "retinol metabolism," and "glycine, serine, and threonine metabolism." Conclusions: The hepatotoxicity of DFS on broiler chickens might be achieved by inducing the apoptosis of hepatocytes and affecting the metabolism of retinol and purine. The present study could provide molecular insights into the hepatotoxicity of DFS on broiler chickens.

• Smart Structures and Systems
• /
• v.30 no.5
• /
• pp.545-556
• /
• 2022

Through the examination of literatures, electronic commerce is a subject which is accepted in enterprises to define e-commerce adoption, trends, and issues that are assisting and obstructing its efficacy. E-commerce offers numerous advantages to consumer satisfaction in any place and helps the company to get a competitive benefit over its competitors. The Internet has expanded the scope of business. Many business information is available by the global network that supports information gathering between organizations, businesses and their clients, while various divisions of a business is increasing at an exponential rate. Meanwhile, there are a few barriers to proper e-commerce usage and adoption, such as reliable internet connections, poor e-commerce supporting infrastructures, logistics systems presenting socio-regulatory and poor transportation barriers and demonstrating the significant improvement of e-commerce reliable and affordable Internet provisions, i.e., Internet cost, intensity, and reasonable level of e-readiness. The operational and strategic significance of information-based virtual value chains for all organizations cannot be emphasized. As a consequence, this study confirms worldwide market elements of e-commerce, such as its issues, benefits, relevance, scope, facilitators and projects prospective obstacles in a developing economy.

• Journal of Venture Innovation
• /
• v.5 no.2
• /
• pp.101-110
• /
• 2022

It is easy for first movers of platform business model to monopolize the market due to the platform's own characteristics such as network effect and flywheel strategy. Accordingly, the regulations on platform operators are constantly being discussed in the recent monopoly regulation arguments, but the concrete regulations have not been settled worldwide. This is because there is no clear consensus on the valuation method which can objectively identify dominant platform firms from the others. This study suggested a platform valuation method based on the Tobin's Q theory, by measuring the moderating effect of the existence of specific scale of platform on the relationship between replacement cost and market valuation. Our method can not only be a standard for settling monopoly regulation by converging the regulation targets, but also contribute to active investment on the new platform firms by evaluating their potential growths quantitatively.

• IMMUNE NETWORK
• /
• v.23 no.5
• /
• pp.37.1-37.11
• /
• 2023

Forkhead box P3-positive (Foxp3⁺)-inducible Tregs (iTregs) are readily generated by TGF-β1 at low TCR signaling intensity. TGF-β1-mediated Foxp3 expression is further enhanced by retinoic acid (RA) and lactoferrin (LF). However, the intensity of TCR signaling required for induction of Foxp3 expression by TGF-β1 in combination with RA and LF is unknown. Here, we found that either RA or LF alone decreased TGF-β1-mediated Foxp3 expression at low TCR signaling intensity. In contrast, at high TCR signaling intensity, the addition of either RA or LF strongly increased TGF-β1-mediated Foxp3 expression. Moreover, decreased CD28 stimulation was more favorable for TGF-β1/LF-mediated Foxp3 expression. Lastly, we found that at high signaling intensities of both TCR and CD28, combined treatment with TGF-β1, RA, and LF induced robust expression of Foxp3, in parallel with powerful suppressive activity against responder T cell proliferation. Our findings that TGFβ/RA/LF strongly generate high affinity Ag-specific iTreg population would be useful for the control of unwanted hypersensitive immune reactions such as various autoimmune diseases.

• IMMUNE NETWORK
• /
• v.23 no.5
• /
• pp.42.1-42.21
• /
• 2023

When the lungs are infected with bacteria, alveolar macrophages (AMs) are recruited to the site and play a crucial role in protecting the host by reducing excessive lung inflammation. However, the regulatory mechanisms that trigger the recruitment of AMs to lung alveoli during an infection are still not fully understood. In this study, we identified a critical role for NADPH oxidase 4 (NOX4) in the recruitment of AMs during Staphylococcus aureus lung infection. We found that NOX4 knockout (KO) mice showed decreased recruitment of AMs and increased lung neutrophils and injury in response to S. aureus infection compared to wildtype (WT) mice. Interestingly, the burden of S. aureus in the lungs was not different between NOX4 KO and WT mice. Furthermore, we observed that depletion of AMs in WT mice during S. aureus infection increased the number of neutrophils and lung injury to a similar level as that observed in NOX4 KO mice. Additionally, we found that expression of intercellular adhesion molecule-1 (ICAM1) in NOX4 KO mice-derived lung endothelial cells was lower than that in WT mice-derived endothelial cells. Therefore, we conclude that NOX4 plays a crucial role in inducing the recruitment of AMs by controlling ICAM1 expression in lung endothelial cells, which is responsible for resolving lung inflammation during acute S. aureus infection.

• IMMUNE NETWORK
• /
• v.24 no.1
• /
• pp.9.1-9.21
• /
• 2024

The cytokine IL-7 plays critical and nonredundant roles in T cell immunity so that the abundance and availability of IL-7 act as key regulatory mechanisms in T cell immunity. Importantly, IL-7 is not produced by T cells themselves but primarily by non-lymphoid lineage stromal cells and epithelial cells that are limited in their numbers. Thus, T cells depend on cell extrinsic IL-7, and the amount of in vivo IL-7 is considered a major factor in maximizing and maintaining the number of T cells in peripheral tissues. Moreover, IL-7 provides metabolic cues and promotes the survival of both naïve and memory T cells. Thus, IL-7 is also essential for the functional fitness of T cells. In this regard, there has been an extensive effort trying to increase the protein abundance of IL-7 in vivo, with the aim to augment T cell immunity and harness T cell functions in anti-tumor responses. Such approaches started under experimental animal models, but they recently culminated into clinical studies, with striking effects in re-establishing T cell immunity in immunocompromised patients, as well as boosting anti-tumor effects. Depending on the design, glycosylation, and the structure of recombinantly engineered IL-7 proteins and their mimetics, recombinant IL-7 molecules have shown dramatic differences in their stability, efficacy, cellular effects, and overall immune functions. The current review is aimed to summarize the past and present efforts in the field that led to clinical trials, and to highlight the therapeutical significance of IL-7 biology as a master regulator of T cell immunity.

• Asia pacific journal of information systems
• /
• v.34 no.1
• /
• pp.150-190
• /
• 2024

This article proposes a framework to elucidate the structural dynamics of the generative AI ecosystem. It also outlines the practical application of this proposed framework through illustrative policies, with a specific emphasis on the development of the Korean generative AI ecosystem and its implications of platform strategies at AI platform-squared. We propose a comprehensive classification scheme within generative AI ecosystems, including app builders, technology partners, app stores, foundational AI models operating as operating systems, cloud services, and chip manufacturers. The market competitiveness for both app builders and technology partners will be highly contingent on their ability to effectively navigate the customer decision journey (CDJ) while offering localized services that fill the gaps left by foundational models. The strategically important platform of platforms in the generative AI ecosystem (i.e., AI platform-squared) is constituted by app stores, foundational AIs as operating systems, and cloud services. A few companies, primarily in the U.S. and China, are projected to dominate this AI platform squared, and consequently, they are likely to become the primary targets of non-market strategies by diverse governments and communities. Korea still has chances in AI platform-squared, but the window of opportunities is narrowing. A cautious approach is necessary when considering potential regulations for domestic large AI models and platforms. Hastily importing foreign regulatory frameworks and non-market strategies, such as those from Europe, could overlook the essential hierarchical structure that our framework underscores. Our study suggests a clear strategic pathway for Korea to emerge as a generative AI powerhouse. As one of the few countries boasting significant companies within the foundational AI models (which need to collaborate with each other) and chip manufacturing sectors, it is vital for Korea to leverage its unique position and strategically penetrate the platform-squared segment-app stores, operating systems, and cloud services. Given the potential network effects and winner-takes-all dynamics in AI platform-squared, this endeavor is of immediate urgency. To facilitate this transition, it is recommended that the government implement promotional policies that strategically nurture these AI platform-squared, rather than restrict them through regulations and stakeholder pressures.

• IMMUNE NETWORK
• /
• v.22 no.3
• /
• pp.21.1-21.21
• /
• 2022

As far the current severe coronavirus disease 2019 (COVID-19), respiratory disease is still the biggest threat to human health. In addition, infectious respiratory diseases are particularly prominent. In addition to killing and clearing the infection pathogen directly, regulating the immune responses against the pathogens is also an important therapeutic modality. Sirtuins belong to NAD+-dependent class III histone deacetylases. Among 7 types of sirtuins, silent information regulator type-1 (SIRT1) played a multitasking role in modulating a wide range of physiological processes, including oxidative stress, inflammation, cell apoptosis, autophagy, antibacterial and antiviral functions. It showed a critical effect in regulating immune responses by deacetylation modification, especially through high-mobility group box 1 (HMGB1), a core molecule regulating the immune system. SIRT1 was associated with many respiratory diseases, including COVID-19 infection, bacterial pneumonia, tuberculosis, and so on. Here, we reviewed the latest research progress regarding the effects of SIRT1 on immune system in respiratory diseases. First, the structure and catalytic characteristics of SIRT1 were introduced. Next, the roles of SIRT1, and the mechanisms underlying the immune regulatory effect through HMGB1, as well as the specific activators/inhibitors of SIRT1, were elaborated. Finally, the multitasking roles of SIRT1 in several respiratory diseases were discussed separately. Taken together, this review implied that SIRT1 could serve as a promising specific therapeutic target for the treatment of respiratory diseases.

• International Journal of Stem Cells
• /
• v.16 no.2
• /
• pp.202-214
• /
• 2023

Background and Objectives: To investigate the role of exosomes from periodontal ligament cells (PDLCs) in bone marrow mesenchymal stem cell (BMSC) migration. Methods and Results: Human PDLCs were applied cyclic tension stretching. Exosomes were extracted from cultured PDLCs by ultracentrifugation, then characterized for their size, morphology and protein markers by NTA, TEM and western blotting. The process that PKH26-labeled exosomes taken up by BMSCs was assessed by confocal microscope. BMSC migration was examined by Transwell assay. Exosomes derived from PDLCs were identified. Cyclic tension stretch application on PDLCs can enhance the migration ability of BMSCs through exosomes. The exosomal miRNA expression profiles of unstretched and stretched PDLCs were tested by miRNA microarray. Four miRNAs (miR-4633-5p, miR-30c-5p, miR-371a-3p and let-7b-3p) were upregulated and six (miR-4689, miR-8485, miR-4655-3p, miR-4672, miR-3180-5p and miR-4476) were downregulated in the exosomes after stretching. Sixteen hub proteins were found in the miRNA-mRNA network. Gene Ontology and KEGG pathway analyses demonstrated that the target genes of differentially expressed exosomal miRNAs closely related to the PI3K pathway and vesicle transmission. Conclusions: The exosomes derived from cyclic tension-stretched PDLCs can promote the migration of BMSCs. Alternation of microRNA profiles provides a basis for further research on the regulatory function of the exosomal miRNAs of PDLCs during orthodontic tooth movement.

• Molecules and Cells
• /
• v.43 no.4
• /
• pp.360-372
• /
• 2020

The basal ganglia network has been implicated in the control of adaptive behavior, possibly by integrating motor learning and motivational processes. Both positive and negative reinforcement appear to shape our behavioral adaptation by modulating the function of the basal ganglia. Here, we examined a transgenic mouse line (G2CT) in which synaptic transmissions onto the medium spiny neurons (MSNs) of the basal ganglia are depressed. We found that the level of collaterals from direct pathway MSNs in the external segment of the globus pallidus (GPe) ('bridging collaterals') was decreased in these mice, and this was accompanied by behavioral inhibition under stress. Furthermore, additional manipulations that could further decrease or restore the level of the bridging collaterals resulted in an increase in behavioral inhibition or active behavior in the G2CT mice, respectively. Collectively, our data indicate that the striatum of the basal ganglia network integrates negative emotions and controls appropriate coping responses in which the bridging collateral connections in the GPe play a critical regulatory role.