• IMMUNE NETWORK
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• v.20 no.4
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• pp.33.1-33.19
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• 2020

We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both T_H1 and T_H2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces T_H2 and T_H17 responses but reduces T_H1 and T_reg responses regardless of adjuvant type, whereas CFA but not alum increased follicular T_H response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

• IMMUNE NETWORK
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• v.20 no.5
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• pp.39.1-39.13
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• 2020

Sjögren's syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration in the exocrine glands. In SS, type I IFN has a pathogenic role, and recently, inflammasome activation has been observed in both immune and non-immune cells. However, the relationship between type I IFN and inflammasome-associated pyroptosis in SS has not been studied. We measured IL-18, caspase-1, and IFN-stimulated gene 15 (ISG15) in saliva and serum, and compared whether the expression levels of inflammasome and pyroptosis components, including absent in melanoma 2 (AIM2), NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and gasdermin E (GSDME), in minor salivary gland (MSG) are related to the expression levels of type I IFN signature genes. Expression of type I IFN signature genes was correlated with mRNA levels of caspase-1 and GSDMD in MSG. In confocal analysis, the expression of caspase-1 and GSDMD was higher in salivary gland epithelial cells (SGECs) from SS patients. In the type I IFN-treated human salivary gland epithelial cell line, the expression of caspase-1 and GSDMD was increased, and pyroptosis was accelerated in a caspase-dependent manner upon inflammasome activation. In conclusion, we demonstrate that type I IFN may contribute to inflammasome-associated pyroptosis of the SGECs of SS patients, suggesting another pathogenic role of type I IFN in SS in terms of target tissue -SGECs destruction.

• IMMUNE NETWORK
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• v.19 no.1
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• pp.7.1-7.11
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• 2019

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder that affects mainly salivary and lacrimal glands, but its cause remains largely unknown. Clinical data indicating that SS occurs in a substantial proportion of patients with lupus points to common pathogenic mechanisms underlying the two diseases. To address this idea, we asked whether SS develops in the lupus-prone mouse strain sanroque (SAN). Owing to hyper-activation of follicular helper T (Tfh) cells, female SAN mice developed lupus-like symptoms at approximately 20 wk of age but there were no signs of SS at that time. However, symptoms typical of SS were evident at approximately 40 wk of age, as judged by reduced saliva flow rate, sialadenitis, and IgG deposits in the salivary glands. Increases in serum titers of SS-related autoantibodies and numbers of autoantibody-secreting cells in cervical lymph nodes (LNs) preceded the pathologic manifestations of SS and were accompanied by expansion of Tfh cells and their downstream effector cells. Thus, our results suggest that chronic dysregulation of Tfh cells in salivary gland-draining LNs is sufficient to drive the development of SS in lupus-prone mice.

• ALGAE
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• v.39 no.1
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• pp.17-30
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• 2024

Red macroalga Pyropia yezoensis is a high valuable cultivated marine crop. Its acclimation to cold stress is especially important for long cultivation period across winter in coasts of warm temperate zone in East Asia. In this study, the response of P. yezoensis thalli to low temperature was analyzed on physiology and transcriptome level, to explore its acclimation mechanism to cold stress. The results showed that the practical photosynthesis activity (indicated by Φ_PSII and qP) was depressed and pigment allophycocyanin content was decreased during the cold stress of 48 h. However, the F_v/F_m and non-photochemical quenching increased significantly after 24 h, and the average growth rate of thalli also rebounded from 24 to 48 h, indicating a certain extent of acclimation to cold stress. On transcriptionally, the low temperature promoted the expression of differentially expressed genes (DEGs) related to carbohydrate metabolism and energy metabolism, while genes related to photosynthetic system were depressed. The increased expression of DEGs involved in ribosomal biogenesis and lipid metabolism which could accelerate protein synthesis and enhance the degree of fatty acid unsaturation, might help P. yezoensis thallus cells to cope with cold stress. Further co-expression network analysis revealed differential expression trends along with stress time, and corresponding hub genes play important roles in the systemic acquired acclimation to cold stress. This study provides basic mechanisms of P. yezoensis acclimation to cold temperature and may aid in exploration of functional genes for genetic breeding of economic macroalgae.

• IMMUNE NETWORK
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• v.24 no.4
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• pp.25.1-25.14
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• 2024

Lupus is characterized by the autoantibodies against nuclear Ags, underscoring the importance of identifying the B cell subsets driving autoimmunity. Our research focused on the mitochondrial activity and CXCR4 expression in CD11c⁺ B cells from lupus patients after ex vivo stimulation with a TLR9 agonist, CpG-oligodeoxyribonucleotide (ODN). We also evaluated the response of CD11c⁺ B cells in ODN-injected mice. Post-ex vivo ODN stimulation, we observed an increase in the proportion of CD11c^hi cells, with elevated mitochondrial activity and CXCR4 expression in CD11c⁺ B cells from lupus patients. In vivo experiments showed similar patterns, with TLR9 stimulation enhancing mitochondrial and CXCR4 activities in CD11c^hi B cells, leading to the generation of anti-dsDNA plasmablasts. The CXCR4 inhibitor AMD3100 and the mitochondrial complex I inhibitor IM156 significantly reduced the proportion of CD11c⁺ B cells and autoreactive plasmablasts. These results underscore the pivotal roles of mitochondria and CXCR4 in the production of autoreactive plasmablasts.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4251-4256
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• 2015

Background: Exposure to cigarette may affect human health and increase risk of a wide range of diseases including pulmonary diseases, such as chronic obstructive pulmonary disease (COPD), asthma, lung fibrosis and lung cancer. However, the molecular mechanisms of pathogenesis induced by cigarettes still remain obscure even with extensive studies. With systemic view, we attempted to identify the specific gene modules that might relate to injury caused by cigarette smoke and identify hub genes for potential therapeutic targets or biomarkers from specific gene modules. Materials and Methods: The dataset GSE18344 was downloaded from the Gene Expression Omnibus (GEO) and divided into mouse cigarette smoke exposure and control groups. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network for each group and detected specific gene modules of cigarette smoke exposure by comparison. Results: A total of ten specific gene modules were identified only in the cigarette smoke exposure group but not in the control group. Seven hub genes were identified as well, including Fip1l1, Anp32a, Acsl4, Evl, Sdc1, Arap3 and Cd52. Conclusions: Specific gene modules may provide better understanding of molecular mechanisms, and hub genes are potential candidates of therapeutic targets that may possible improve development of novel treatment approaches.

• Journal of Hospice and Palliative Care
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• v.19 no.4
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• pp.292-295
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• 2016

Hospice and palliative care in Taiwan has been growing continuously. The 2015 Quality of Death index, as rated by the Economist Intelligence Unit, ranked Taiwan first among Asian countries and sixth in the world. In this review article, we highlight three particular areas that might have contributed to this success; the laws and regulations, spiritual care and research network. Finally, we discuss the future challenges and prospects for Taiwanese encounters. A systemic review was conducted with the keywords "hospice palliative care Taiwan" using PubMed. The passing of the "Natural Death Act" in 2000 set the example and established a landmark for patient autonomy in Asia; it guarantees the patient's right to request that medical staff do not resuscitate (DNR) them and to reject other futile medical treatments at the end of their life, thus reflecting the importance of palliative care from the policy perspective. In 2015, Taiwan passed another pioneering law entitled the "Patient Autonomy Act". This law states that a patient may decline medical treatment according to his/her own will. Taiwanese indigenous spiritual care was launched in 2000. It requires a Buddhist Chaplain to successfully complete a training program consisting of lectures, as well as bedside practicum before applying Buddhist practices to end-of-life care. The Japan-Korea-Taiwan research network was established for the purpose of enabling collaborative research for the East-Asian collaborative cross-cultural Study to Elucidate the Dying process (EASED) cohort. With consensus from the government and society to make it a priority, hospice and palliative medicine in Taiwan has been growing steadily.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.5
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• pp.367-379
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• 2019

Although atopic dermatitis (AD) is known to be a representative skin disorder, it also affects the systemic immune response. In a recent study, myoblasts were shown to be involved in the immune regulation, but the roles of muscle cells in AD are poorly understood. We aimed to identify the relationship between mitochondria and atopy by genome-wide analysis of skeletal muscles in mice. We induced AD-like symptoms using house dust mite (HDM) extract in NC/Nga mice. The transcriptional profiles of the untreated group and HDM-induced AD-like group were analyzed and compared using microarray, differentially expressed gene and functional pathway analyses, and protein interaction network construction. Our microarray analysis demonstrated that immune response-, calcium handling-, and mitochondrial metabolism-related genes were differentially expressed. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology pathway analyses, immune response pathways involved in cytokine interaction, nuclear factor-kappa B, and T-cell receptor signaling, calcium handling pathways, and mitochondria metabolism pathways involved in the citrate cycle were significantly upregulated. In protein interaction network analysis, chemokine family-, muscle contraction process-, and immune response-related genes were identified as hub genes with many interactions. In addition, mitochondrial pathways involved in calcium signaling, cardiac muscle contraction, tricarboxylic acid cycle, oxidation-reduction process, and calcium-mediated signaling were significantly stimulated in KEGG and Gene Ontology analyses. Our results provide a comprehensive understanding of the genome-wide transcriptional changes of HDM-induced AD-like symptoms and the indicated genes that could be used as AD clinical biomarkers.

• International Journal of Computer Science & Network Security
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• v.22 no.7
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• pp.213-219
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• 2022

Building Ukraine as an independent, sovereign state requires the education of a citizen-patriot, able to live and work in a democracy, ensure the unity of Ukraine, feel constant responsibility for themselves, their people, country, seek to make a real contribution to the reform process. Modern modernization of the education system requires the search for new information and communication technologies that can ensure the formation of a citizen with an active civic position, which involves not only students mastering the rights and responsibilities of citizens, convincing them of the feasibility of democratic transformation of society, patriotic qualities and feelings, but also the identification of motivated civic actions. The pandemic and hostilities have led to significant changes in the field of education around the world, they have caused educational problems in Ukraine. At the beginning of the quarantine in the spring of 2020, all educational institutions in the emergency mode switched to distance learning. Intensive use of information and communication technologies in the life of modern society has led to a rethinking of the content of education and training of future professionals: the main role is played not so much by the information itself as the ability to work with it, critically comprehend and produce new knowledge; the main thing is not the amount of information, but its quality; information is needed for further practical application and transformation into knowledge, and the ability to work with information becomes one of the important competencies of the modern specialist in the new transformation of society: from information to the knowledge society. In this context, one of the main forms of training is distance learning, which is able to respond to the challenges of society. The main methodological positions that are taken into account in the construction of the structure and dynamics of the formation of civic responsibility of the individual during the use of information and communication technologies are highlighted. The structure of civil responsibility as a holistic system of information and communication technologies is outlined, which includes three subsystems that characterize the natural, social and systemic qualities of citizenship, interconnected hierarchically and synergistically.The constituent elements of the structural part of the model of civic culture of the individual are analyzed.

• International Journal of Computer Science & Network Security
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• v.22 no.11
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• pp.272-278
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• 2022

The article proves the idea that the protection and development of Ukraine as an independent, sovereign state requires the education of a patriot citizen who is able to live and work in a democracy, ensure the unity of Ukraine, feel constant responsibility for himself, his people, the country, and strive to make a real contribution to reform processes, especially in unstable, wartime. The main goal of educational institutions in the system of educational work of the modern information space is revealed. The tasks of patriotic education of the individual are presented. The content of patriotic education at the wartime stage and the main characteristics of the content of patriotism are substantiated. The main methodological positions that are taken into account in the construction of the structure and dynamics of the formation of civil responsibility of the individual are highlighted. The structure of civic responsibility as an integral system of the modern information space is drawn, which includes three subsystems that characterize the natural, social and systemic qualities of citizenship, interconnected hierarchically and synergistically. The components of the structural part of the model of civil culture of the individual in the modern information space are analyzed.Modern modernization of the education system in the modern information space, which has led to the emergence of a new type of Educational Institutions, requires the search for new pedagogical technologies that can ensure the formation of a patriotic citizen with an active civic position, which involves not only mastering students' knowledge about the rights and obligations of citizens, convincing them of the expediency of democratic transformations of society, the formation of high moral and strong-willed, patriotic qualities and feelings, but also identifying motivated civic actions, actions that are necessary during martial law in Ukraine.