• Title/Summary/Keyword: Systemic Model

Search Result 417, Processing Time 0.027 seconds

Comparative evaluation to select optimal adjuvant of novel type Salmonella Typhimurium inactivated bacteria for protecting Salmonella infections in a murine model (마우스에서 살모넬라 감염증 예방을 위한 신개념 Salmonella Typhimurium 불활화 사균체에 최적 adjuvant 선택을 위한 효능 비교 시험)

  • Moon, Ja-Young;Ochirkhuyag, Enkhsaikhan;Kim, Won-Kyong;Lee, Jun-Woo;Jo, Young-Gyu;Kwak, Kil Han;Park, Byung Yong;Hur, Jin
    • Korean Journal of Veterinary Service
    • /
    • v.43 no.2
    • /
    • pp.89-97
    • /
    • 2020
  • This study was carried out to examine a novel inactivated Salmonella Typhimurium (S. Typhimurium) vaccine candidate for protection of mice against salmonellosis by immunization of BALB/c mice using various type adjuvant. The novel type-inactivated vaccine candidate was constructed by adding Chlorhexidine digluconate solution. BALB/c mice were divided into 6 groups of 15 mice apiece. The mice were intramuscularly (IM) primed at 6 weeks of age and were IM boosted 8 weeks of age. Groups A and B mice were injected with sterile phosphate-buffered saline as controls; group C mice were inoculated with 5×108 cells/100 µL of formalin-inactivated S. Typhimurium cells and adjuvant ISA70; groups D~F mice were immunized with 5×108 cells/100 µL of the inactivated vaccine candidate and adjuvant ISA70, adjuvant IMS1313 and adjuvant IMS1313 containing 30 ㎍/mL of GI24, respectively. All mice (except group A mice) were orally challenged with a virulent S. Typhimurium strain at 10 weeks of age. Mice from groups C-F had significantly increased IgG levels compared to control groups (A-B) mice. The levels of splenocyte IFN-γ and IL-4 in mice of all groups were measured by ELISA, resulting in increased immunity in group F mice compared to those of groups A-E mice. These data suggested that systemic and cell-mediated immune responses were highly induced by IM immunization with the vaccine candidate and adjuvant IMS1313 containing GI24. Furthermore, clinical signs such as death were observed in only 20% of group F mice after virulent Salmonella strain challenge, however, groups B and C (100%), and groups D and E (60%) mice died. This data suggested that mice immunized by intramuscular prime and booster with this vaccine candidate and adjuvant IMS1313 containing GI24 effectively protected mice from salmonellosis.

Effects of Geiji-Bokryung-Hwan on eNOS, nNOS, Caveolin-1 and bFGF Protein Expressions and the Endothelial Cells of the Corpus Cavernosum in Hypercholesterolemic Rat

  • Kim Jae-Woo;Son Soo-Gon;Sa Eun-Ho;Kim Cherl-Ho;Park Won-Hwan
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.20 no.1
    • /
    • pp.174-180
    • /
    • 2006
  • We examine the effect of Geiji-Bokryung-Hwan(GBH) on erectile function in a rat model of hypercholesterolemic erectile dysfunction. GBH, a drug preparation consisting of five herbs of Cinnamomi Ramulus (Geiji), Poria Cocos (Bokryun), Mountan Cortex Radicis (Mokdanpi), Paeoniae Radix (Jakyak), and Persicae Semen (Doin) is a traditional Korean herbal medicine that is widely used in the treatment of atherosclerosis-related disorders. In this study, 3-month-old Sprague-Dawley rats were used. The 6 rats control animals were fed a normal diet and the other 18 rats were fed 1% cholesterol diet for 3 months. After 1 months, GBH was added to the drinking water of the treatment group of 12 rats but not the cholesterol only group of 6 rats. Of the 12 rats 6 received 30 mg/kg per day (group 1) and 6 received 60 mg/kg per day (group 2) of GBH. At 3 months erectile function was evaluated with cavernous nerve electrostimulation in all animals. Penile tissues were collected for electron microscopy, and to perform Western blot for endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), basic fibroblast growth factor (bFGF) and caveolin-1. Systemic arterial pressure was not significantly different between the animals that were fed the 1% cholesterol diet and the controls. Conversely erectile function was not impaired in the herbal medicine treated rats. Electron microscopy showed many caveolae with fingerlike processes in the cavernous smooth muscle and endothelial cell membranes in control and treated rats but not in the cholesterol only group of rats. Western blot showed differences among groups in protein expression for eNOS, nNOS, caveolin-1 and bFGF protein expression in penile tissue. Increased eNOS and nNOS protein expressions dy high cholesterol diet were significantly decreased in group 1 and group 2. Interestingly, caveolin-1 and bFGF protein expression was significantly higher in groups 1 and 2 than in the cholesterol only and control groups.

Gender-independent efficacy of mesenchymal stem cell therapy in sex hormone-deficient bone loss via immunosuppression and resident stem cell recovery

  • Sui, Bing-Dong;Chen, Ji;Zhang, Xin-Yi;He, Tao;Zhao, Pan;Zheng, Chen-Xi;Li, Meng;Hu, Cheng-Hu;Jin, Yan
    • Experimental and Molecular Medicine
    • /
    • v.50 no.12
    • /
    • pp.12.1-12.14
    • /
    • 2018
  • Osteoporosis develops with high prevalence in both postmenopausal women and hypogonadal men. Osteoporosis results in significant morbidity, but no cure has been established. Mesenchymal stem cells (MSCs) critically contribute to bone homeostasis and possess potent immunomodulatory/anti-inflammatory capability. Here, we investigated the therapeutic efficacy of using an infusion of MSCs to treat sex hormone-deficient bone loss and its underlying mechanisms. In particular, we compared the impacts of MSC cytotherapy in the two genders with the aim of examining potential gender differences. Using the gonadectomy (GNX) model, we confirmed that the osteoporotic phenotypes were substantially consistent between female and male mice. Importantly, systemic MSC transplantation (MSCT) not only rescued trabecular bone loss in GNX mice but also restored cortical bone mass and bone quality. Unexpectedly, no differences were detected between the genders. Furthermore, MSCT demonstrated an equal efficiency in rectifying the bone remodeling balance in both genders of GNX animals, as proven by the comparable recovery of bone formation and parallel normalization of bone resorption. Mechanistically, using green fluorescent protein (GFP)-based cell-tracing, we demonstrated rapid engraftment but poor inhabitation of donor MSCs in the GNX recipient bone marrow of each gender. Alternatively, MSCT uniformly reduced the $CD3^+T$-cell population and suppressed the serum levels of inflammatory cytokines in reversing female and male GNX osteoporosis, which was attributed to the ability of the MSC to induce T-cell apoptosis. Immunosuppression in the microenvironment eventually led to functional recovery of endogenous MSCs, which resulted in restored osteogenesis and normalized behavior to modulate osteoclastogenesis. Collectively, these data revealed recipient sexually monomorphic responses to MSC therapy in gonadal steroid deficiency-induced osteoporosis via immunosuppression/anti-inflammation and resident stem cell recovery.

Effects of ibuprofen-loaded TiO2 nanotube dental implants in alloxan-induced diabetic rabbits

  • Kim, Young-Gyo;Kim, Wan-Tae;Jung, Bo Hyun;Yoo, Ki-Yeon;Um, Heung-Sik;Chang, Beom-Seok;Lee, Jae-Kwan;Choi, Won-Youl
    • Journal of Periodontal and Implant Science
    • /
    • v.51 no.5
    • /
    • pp.352-363
    • /
    • 2021
  • Purpose: Some systemic conditions, especially diabetes mellitus (DM), adversely affect dental implant success. This study aimed to investigate the effects of ibuprofen-loaded TiO2 nanotube (ILTN) dental implants in alloxan-induced diabetic rabbits. Methods: Twenty-six New Zealand white rabbits were treated with alloxan monohydrate to induce DM. At 2 weeks following DM induction, 3 types of implants (sandblasted, large-grit, and acid-etched [SLA], ILTN, and machined) were placed into the proximal tibia in the 10 rabbits that survived following DM induction. Each type of implant was fitted randomly in 1 of the holes (round-robin method). The animals were administered alizarin (at 3 weeks) and calcein (at 6 weeks) as fluorescent bone markers, and were sacrificed at 8 weeks for radiographic and histomorphometric analyses. Results: TiO2 nanotube arrays of ~70 nm in diameter and ~17 ㎛ in thickness were obtained, and ibuprofen was loaded into the TiO2 nanotube arrays. A total of 26 rabbits were treated with alloxan monohydrate and only 10 rabbits survived. The 10 surviving rabbits showed a blood glucose level of 300 mg/dL or higher, and the implants were placed in these diabetic rabbits. The implant stability quotient (ISQ) and bone-to-implant contact (BIC) values were significantly higher in the ILTN group (ISQ: 61.8, BIC: 41.3%) and SLA group (ISQ: 62.6, BIC: 46.3%) than in the machined group (ISQ: 53.4, BIC: 20.2%), but the difference in the BIC percentage between the SLA and ILTN groups was not statistically significant (P=0.628). However, the bone area percentage was significantly higher in the ILTN group (78.0%) than in the SLA group (52.1%; P=0.000). Conclusions: The: ILTN dental implants showed better stability (ISQ) and BIC than the machined implants; however, these values were similar to the commercially used SLA implants in the 2-week diabetic rabbit model.

Profiling of remote skeletal muscle gene changes resulting from stimulation of atopic dermatitis disease in NC/Nga mouse model

  • Lee, Donghee;Seo, Yelim;Kim, Young-Won;Kim, Seongtae;Choi, Jeongyoon;Moon, Sung-Hee;Bae, Hyemi;Kim, Hui-sok;Kim, Hangyeol;Kim, Jae-Hyun;Kim, Tae-Young;Kim, Eunho;Yim, Suemin;Lim, Inja;Bang, Hyoweon;Kim, Jung-Ha;Ko, Jae-Hong
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.23 no.5
    • /
    • pp.367-379
    • /
    • 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.

Systemically administered neurotensin receptor agonist produces antinociception through activation of spinally projecting serotonergic neurons in the rostral ventromedial medulla

  • Li, Yaqun;Kang, Dong Ho;Kim, Woong Mo;Lee, Hyung Gon;Kim, Seung Hoon;You, Hyun Eung;Choi, Jeong Il;Yoon, Myung Ha
    • The Korean Journal of Pain
    • /
    • v.34 no.1
    • /
    • pp.58-65
    • /
    • 2021
  • Background: Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. Methods: Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague-Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. Results: Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. Conclusions: These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.

The Use of Information and Communication Technologies in Education of Students' Civic Responsibility

  • Sadovyi, Mykola;Terenko, Olena;Filimonova, Tetiana;Malanchuk, Serhii;Vovkochyn, Lyudmyla;Paslawska, Alla;Oros, Ildiko
    • International Journal of Computer Science & Network Security
    • /
    • v.22 no.7
    • /
    • pp.213-219
    • /
    • 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.

The Main Methodological Positions of Educational Institutions in the System of Educational Work of the Modern Information Space

  • Shumiatska, Oleksandra;Palamar, Nataliia;Bilyk, Ruslana;Yakymenko, Svitlana;Yakovenko, Serhii;Tsybulko, Liudmyla;Bida, Olena
    • International Journal of Computer Science & Network Security
    • /
    • v.22 no.11
    • /
    • pp.272-278
    • /
    • 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.

The Effect of Ampelopsis japonica (Thunb.) Makino on Osteoclastogenesis and Expression of Osteoclast-Related Gene (백렴(白蘞)의 파골세포 분화 및 관련 유전자 발현 억제에 미치는 영향)

  • Hongsik Kim;Sumin Lee;Minsun Kim;Jae-Hyun Kim;Yejin Kang;Seoung Jun Kwon;Youngwoo Nam;Seungwoo Yoo;Hong-Seok Choi;SeonJin Huh;Youngjoo Sohn;Hyuk-Sang Jung
    • The Korea Journal of Herbology
    • /
    • v.38 no.5
    • /
    • pp.9-19
    • /
    • 2023
  • Objectives : Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density and increased risk of fractures. Bisphosphonates and selective estrogen receptors, which are bone resorption inhibitors that are currently widely used as osteoporosis treatments, show serious side effects when administered for a long time. Research on bone resorption inhibitors that complement the problems of existing treatments is needed. The purpose of this study was to investigate the effect of inhibiting osteoclast differentiation and activity on the tuberous root of Ampelopsis japonica (Thunb.) Makino (AM). Methods : After extracting AM using distilled water and ethanol, the inhibitory effects of the two solvents on osteoclast differentiation were compared using the RANKL-induced in vitro experimental model and the TRAP assay kit. The impact of AM on bone resorption was investigated through the pit formation assay, and its effect on F-actin formation was assessed through fluorescent staining. Additionally, protein and mRNA expression levels of osteoclast differentiation markers (NFATc1, c-Fos, TRAP and ATP6v0d2) and resorption markers (MMP-9, CTK, and CA2) were analyzed via western blot and RT-PCR. Results : AM treatment significantly decreased the number of TRAP-positive cells and pit formation area. Furthermore, AM suppressed both the protein and mRNA expression of NFATc1 and c-Fos, key transcription factors involved in osteoclast differentiation and it downregulated the expression of osteoclast-associated genes such as TRAP, CTK, MMP-9, CA2, and ATP6v0d2. Conclusions : These results suggest that AM can inhibit bone resorption and osteoclast differentiation, indicating its potential for use in the treatment and prevention of osteoporosis.

Purple perilla frutescens extracts containing α-asarone inhibit inflammatory atheroma formation and promote hepatic HDL cholesterol uptake in dyslipidemic apoE-deficient mice

  • Sin-Hye Park;Young Eun Sim;Min-Kyung Kang;Dong Yeon Kim;Il-Jun Kang;Soon Sung Lim;Young-Hee Kang
    • Nutrition Research and Practice
    • /
    • v.17 no.6
    • /
    • pp.1099-1112
    • /
    • 2023
  • BACKGROUND/OBJECTIVES: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis. MATERIALS/METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk. RESULTS: The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice. CONCLUSIONS: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.