• Title/Summary/Keyword: Loss-differentiation

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Comparison of Cerebral Cortex Transcriptome Profiles in Ischemic Stroke and Alzheimer's Disease Models

  • Juhyun Song
    • Clinical Nutrition Research
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    • v.11 no.3
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    • pp.159-170
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    • 2022
  • Ischemic stroke and Alzheimer's disease (AD) are representative geriatric diseases with a rapidly increasing prevalence worldwide. Recent studies have reported an association between ischemic stroke neuropathology and AD neuropathology. Ischemic stroke shares some similar characteristics with AD, such as glia activation-induced neuroinflammation, amyloid beta accumulation, and neuronal cell loss, as well as some common risk factors with AD progression. Although there are considerable similarities in neuropathology between ischemic stroke and AD, no studies have ever compared specific genetic changes of brain cortex between ischemic stroke and AD. Therefore, in this study, I compared the cerebral cortex transcriptome profile of 5xFAD mice, an AD mouse model, with those of middle cerebral artery occlusion (MCAO) mice, an ischemic stroke mouse model. The data showed that the expression of many genes with important functional implications in MCAO mouse brain cortex were related to synaptic dysfunction and neuronal cell death in 5xFAD mouse model. In addition, changes in various protein-coding RNAs involved in synaptic plasticity, amyloid beta accumulation, neurogenesis, neuronal differentiation, glial activation, inflammation and neurite outgrowth were observed. The findings could serve as an important basis for further studies to elucidate the pathophysiology of AD in patients with ischemic stroke.

Spring Freezing Injuries and Their Effects on Yield of Barley (Hordeum vulgare L.) and Wheat (Triticum aestivum L.) (봄철 저온장해가 맥류 수량에 미치는 영향)

  • Koo, Bon-Cheol;Park, Moon-Woong;Kim, Ki-Jun;An, Jong-Guk
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.52 no.1
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    • pp.17-28
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    • 2007
  • To understand the spring freezing injury symptoms during sensitive growth stage and yield loss of barley and wheat, field tests were done by using vinyl mulching and natural cold weather. The growth stage sensitive were booting, spikelet differentiation and flower organ development stages for both crops. However, barley and wheat differed in their growth responses, in that barley was less affected than wheat. For instance, barley recorded 28 percent dead ears, 10 percent dead plants and 18 percent ear degenerations while wheat recorded higher values of 59 percent, 44 percent and 44 percent, respectively. Although there were no recorded froze-resistant varieties in both barley and wheat, some showed tolerance as their yields were not affected by freezing stress. The 'Chalbori' cultivars of barley and 'Geurumil' and 'Chokwang' cultivars of wheat recorded steady yields. The yield components of barley and wheat that were greatly affected by freezing stress were the number of spike per square and the number of grain per spike. The major cause of yield loss in Suwon 259 and Kangbori was the number of spike per square but not the number of grain per spike. The study showed, however, that both the number of spike per square and the number of grain per spike were vulnerable to freezing and that which contribute much to yield loss of barley and wheat.

Impact on Inflammation and Recovery of Skin Barrier by Nordihydroguaiaretic Acid as a Protease-Activated Receptor 2 Antagonist

  • Kim, Hyo-Young;Goo, Jung-Hyun;Joo, Yeon-Ah;Lee, Ha-Yoen;Lee, Se-Mi;Oh, Chang-Taek;Ahn, Soo-Mi;Kim, Nam-Hoon;Hwang, Jae-Sung
    • Biomolecules & Therapeutics
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    • v.20 no.5
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    • pp.463-469
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    • 2012
  • Atopic dermatitis is a chronic, inflammatory disease of the skin with increased transepidermal water loss. Both an abnormal inflammatory response and a defective skin barrier are known to be involved in the pathogenesis of atopic dermatitis. Protease activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$. PAR2 is expressed in suprabasal layers of the epidermis and regulates inflammatory responses and barrier homeostasis. In this study, we show that nordihydroguaiaretic acid (NDGA) inhibits the PAR2-mediated signal pathway and plays a role in skin barrier recovery in atopic dermatitis. Specifically, NDGA reduces the mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes by down-regulating inflammatory mediators, such as interleukin-8, thymus and activation-regulated chemokine and intercellular cell adhesion molecule-1 in HaCaT keratinocytes. Also, NDGA decreases the protein expression of involucrin, a differentiation maker of keratinocyte, in both HaCaT keratinocytes and normal human epidermal keratinocytes. We examined NDGA-recovered skin barrier in atopic dermatitis by using an oxazolone-induced atopic dermatitis model in hairless mice. Topical application of NDGA produced an increase in transepidermal water loss recovery and a decrease in serum IgE level, without weight loss. Accordingly, we suggest that NDGA acts as a PAR2 antagonist and may be a possible therapeutic agent for atopic dermatitis.

Acer tegmentosum Maxim Prevents Bone Loss by Inhibiting Osteoclastogenesis and Promoting Osteoblast Mineralization in Ovariectomized Mice

  • Oh, Tae Woo;Park, Kwang-Il;Do, Hyun Ju;Kim, Kyungho;Yang, Hye Jin;Cho, Won Kyung;Ma, Jin Yeul
    • Natural Product Sciences
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    • v.26 no.1
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    • pp.83-89
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    • 2020
  • Osteoporosis is a worldwide disease leading to significant economic and societal burdens globally. Osteoporosis is caused by unbalanced bone remodeling between the rate of osteoclast bone resorption and osteoblast bone formation. Acer tegmentosum Maxim (AT) is a traditional herbal medicine containing multiple biological activities such as anti-oxidant and anti-inflammatory purposes. However, its role in osteoporosis has not been fully studied. Therefore, we investigated whether AT has a potent inhibitory effect on osteoporosis and its mechanism through a systemic evaluation in ovariectomized (OVX) mice. OVX mice were orally administrated with the AT at doses of 50, 100, and 200 mg/kg for 10 weeks. Histological images and histomorphometry analyses were performed by H&E and Toluidine blue satin, and the expression levels of receptor activator for nuclear factor-kB ligand (RANKL), nuclear factor of activated T cells cytoplasm 1 (NFATc1), c-Fos, and matrix metalloproteinase 9 (MMP9) related to the osteoclast differentiation were investigated using immunohistochemical analysis. Administration of AT prevented bone loss and the alternations of osteoporotic bone parameters at the distinct regions of the distal femur and spongiosa region in OVX mice. Further, administration of AT increased periosteal bone formation in a dose-dependent manner. Meanwhile, AT inhibited not only the expression of NFATc1 and c-Fos, which are two major regulators of osteoclastogenesis but also reduced bone resorbed encoding expression of MMP9 and RANKL. Our results indicated that administration of AT prevented bone loss and the alternations of osteoporotic bone parameters at the distinct regions of the distal femur and spongiosa region in OVX mice. Also AT has the bone protective effect through the suppression of osteoclast and promotion of osteoblast, suggesting that it could be a preventive and therapeutic candidate for anti-osteoporosis.

Distribution and Differentiation of the Choline Acetyltransferase-immunoreactive Nerve Cells in the Basal Nucleus of Meynert of the Rat Forebrains During the Postnatal Development (흰쥐 출생후 발생에 따른 전뇌 기저부 Meynert기저핵에서 Choline Acetyltranseferase 면역반응 신경세포의 분포 및 분화)

  • Lee, Nam-Seob;Chung, Young-Wha
    • Applied Microscopy
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    • v.29 no.4
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    • pp.479-491
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    • 1999
  • This study was performed to investigate the distribution and differentiation of choline acetyltransferase (ChAT)-immunoreactive cells in the basal nucleus of Meynert of the postnatal and adult rat forebrains, utilizing techniques of immunocytochemistry. According to the cell shape and the ratio of long axis vs short axis of cell soma, the ChAT-immunoreactive nerve cells in the basal nucleus of Meynert of the adult rat were classified into six types. In the adult rat, the frequency distributions (FD) of round, oval, elongated, fusiform, triangular and polygonal cells were 9.4%, 35.5%, 32.1%, 5.9%, 9.1% and 8.0%, respectively. The FD of oval and round nerve cells on the postnatal day (PND) 14 were observed to be 18.7% and 51.5%, respectively. Those were shown to be progressively decreased during developmental process to the adult. Also, those of elongated and triangular nerve cells on the PND 21 were observed to be 30.4% and 10.1%, respectively. Those were shown to be same phenomenon a,1 those in the round and oval cells. Meanwhile, those of the triangular and polygonal nerve cells were progressively increased from the early postnatal stage to the adult. The total mean volumes of ChAT-immunoreactive cell somata in the PND 7 rat were the lowest $(1,083{\mu}m^3)$ and those in the PND 21 rat were shown to be the highest $(5,045{\mu}m^3)$. But in the adult, those were decreased to $(2,731{\mu}m^3)$. Those in the PND 21 rat were shown to be about 84.7% larger than those in the adult. On the electron micrography, the cell organelles such as ribosomes, polysomes, rough endoplasmic reticula (RER) and mitochondria were well developed in the PND 21 rat forebrains, but Golgi complexes were shown to be proliferating phase. Especially, ribosomes, polysomes and RER were immunoreactive in the tissues treated with 0.05% triton X-100. According to the observations in the present study, it is considered that the ChAT-immunoreactive nerve cells in the basal nucleus of Meynert of the rat forebrains are differentiated throughout the following processes of changes during the postnatal development: 1) increase of cell soma volumes with the differentiation of tell organelles and neurites, 2) increase in the FD of differentiated tell types and 3) cell schrinkage without cell loss. The ribosomes, polysomes and RER are considered to be closely related to the intracellular localization and biosynthesis of the ChAT but not Colgi complex.

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EFFECT OF THE NUCLEAR FACTOR I-C ON THE FORMATION OF HERTWIG'S EPITHELIAL ROOT SHEATH DURING ROOT DEVELOPMENT (Nuclear factor I-C가 치근발생 과정에서 Hertwig's 상피초 형성에 미치는 영향)

  • Shin, In-Cheol;Park, Joo-Cheol;Jeong, Moon-Jin;Oh, Hyun-Ju;Park, Sun-Hwa;Lee, Chang-Seop;Kim, Heung-Joong
    • Journal of the korean academy of Pediatric Dentistry
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    • v.32 no.3
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    • pp.576-583
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    • 2005
  • Tooth formation is a complex developmental process that is mediated through a series of reciprocal epithelial-mesenchymal interactions. Several signal pathways and transcription factors have been implicated in regulating molar crown development, but relatively little is known about the regulation of root development. It was reported that NFI-C knockout mice showed abnormal root formation with normal crown. The aims of this study are to elucidate how the NFI-C regulate the determine of root shape and odontoblasts differentiation. We carried out immunohistochemistry using cytokeratin to investigate the role of Hertwig's epithelial root sheath and DSPP mRNA in-situ hybridization to conform the nature of root dentin during root development in NFI-C knockout mice. Cytokeratin reacted with all the HERS cells and the continuity of cytokeratin positive cells between the HERS cells and enamel epithelium was lost in the cervical region both wild and K/O types. After root dentin deposition cytokeratin positive-HERS cells showed irregularity and loss of polarity in the cervical region in K/O type. DSPP mRNA was strongly expressed in odontoblasts of crown and root dentin in wild type mice, whereas expression of DSPP mRNA was restricted in odontoblast of crown dentin in the K/O type. During root formation in NFI-C knockout mice, HERS normally grow out of the crown but fail to induce odontoblast differentiation in root portion. These results suggest that NFI-C may play important roles in odontoblast differentiation during root dentin formation.

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Beneficial Effect of Curcumin on Epidermal Permeability Barrier Function in Hairless Rat (무모쥐에서 자외선에 의한 피부 장벽 손상에 미치는 커큐민의 보호 효과)

  • Jeon, Hee-Young;Kim, Jeong-Kee;Kim, Wan-Gi;Lee, Sang-Jun
    • Korean Journal of Food Science and Technology
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    • v.40 no.6
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    • pp.686-690
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    • 2008
  • Recent research has shown that curcumin has beneficial effects in a variety of skin diseases, including scleroderma, psoriasis, and skin cancer. In this study, we assessed the effects of curcumin on epidermal permeability barrier function in vivo and in vitro. In order to evaluate the effects of curcumin on epidermal permeability barrier function in vivo, hairless rats were exposed to UVB irradiation, and curcumin was administered orally at a dosage of 150 mg/kg per day for 8 weeks. Transepidermal water loss (TEWL) and epidermal thickness were measured at the end of the experiment. The expression of filaggrin, a marker of keratinocyte differentiation, and serine palmitoyltransferase (SPT), a marker of the formation of the stratum corneum lipid barrier, in human HaCat keratinocytes were analyzed. The in vivo results showed that an 8 week administration of curcumin markedly prevented the UVB-induced increase in TEWL. The UV-induced increase in epidermal thickness was also reduced significantly by curcumin treatment. The in vitro results demonstrated the concentration-dependent effects of curcumin on the expression of both filaggrin and SPT in HaCat cells, reflecting the notion that curcumin can induce epidermal keratinocyte differentiation and can improve the recovery of skin barrier functions. These results show that curcumin is a promising candidate for the improvement of epidermal permeability barrier function.

Study on Development of Assessment Guideline and Endpoints for Clinical Trial with Antitumor Natural Products (천연물 항암제제 임상시험 평가지표 개발연구)

  • Namgung, Mi-Ae;Chang, Yoo-Sung;Jeong, Seung-Gi;Kim, Jin-Seung;Yoon, Sung-Woo;Jang, Ki-Young;Yoo, Hwa-Seung;Jung, Myeon-Woo;Lee, Sung-Ho;Kim, Sung-Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1678-1727
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    • 2006
  • This study was perfromed to develop the assessment guideline and endpoints for clinical trial with anticancer herbal medicine. The botanical products used to humans for long time may be applied to phase 3 clinical trial after submitting the evidences for safety and efficacy of them or completion of basic requirement of phase 1 and phase 2 for safety confirmation and dose determination. Syndrome improvement was chiefly evaluated by Zubrod and karnofsky(%) methods. We suggest the general clinical trial assessment with botanical products, by following assessment points, that is, tumor size for 50 points, survival fate for 10 points, major syndromes for 40 points. It is recommendable that the each symptom of Qi deficiency syndrome, blood deficiency syndrome and Qi stagnation syndrome was allocated by assessment points, Similarly, the each symptom was given the assessment points according to the severity of symptom, for example, slight for 3 points, moderate for 2 points and severe for 1 point in hepatocelluar carcinoma and lung cancer. Then, the efficacy of botanical products was evaluated by the difference between pre-treatment and post-treatment. Asking the neoplastic patients of questionnaire on physical, emotional, cognitive, social and role subjects availability, three more syndromes (Fatigue, Pain and Nausea/Vomit), quality of life(QOL) will be evaluated by GLM statistics. In addition, in case of lung cancer, 13 questions will be asked by the EORTC QLQ-C13 forms. As the assessment of endpoints for efficacy to reduce side effects induced by chemotherapy and radiotherapy, the data of image scanning and hemato-urinalysis can be usefully applied on immune response, weight loss, indigestion, hemopoietic damage and injury of liver and kidney, while the changes of syndromes of side effect can be evaluated by differentiation methods of Qi and blood and five viscera. However, it is still necessary to determine the ratio between scientific analytical method and Oriental differentiation method as well as confirm the Oriental assessment endpoints by clinical trial. In addition, we suggest the continuous development of assessment endpoints on other carcinomas except of hepatocelluar carcinoma and lung cancer in future.

Pathophysiology and MRI Findings of Infectious Spondylitis and the Differential Diagnosis (감염성 척추염과 감별질환의 병태생리와 MRI 소견)

  • Sunjin Ryu;Yeo Ju Kim;Seunghun Lee;Jeongah Ryu;Sunghoon Park;Jung Ui Hong
    • Journal of the Korean Society of Radiology
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    • v.82 no.6
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    • pp.1413-1440
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    • 2021
  • On MRI, abnormal signals of the intervertebral disc, destruction of the upper and lower vertebral body endplate around the disc, and bone marrow edema around the endplate are considered typical findings of infectious spondylitis. These findings can also appear in various non-infectious spinal diseases, such as degenerative changes, acute Schmorl's node, spondyloarthropathy, synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO), chronic recurrent multifocal osteomyelitis, and calcium pyrophosphate dihydrate crystal deposition disease. The imaging findings of infectious spondylitis that can be differentiated from these non-infectious spinal diseases on MRI are high signal intensity and abscess of the disc space, an abscess in the paraspinal soft tissue, and the loss of the linear low signal intensity on T1-weighted images of the bony endplate. However, these differentiation points do not always apply since there are many similarities in the imaging findings of infectious and non-infectious diseases. Therefore, for an accurate diagnosis, it is important to know the imaging characteristics related to the pathophysiology of not only infectious spondylitis but also non-infectious spinal diseases, which requires differentiation from infection.

Induction of Apoptosis in Arsenic Trioxide-treated Lung Cancer A549 Cells by Buthionine Sulfoximine

  • Han, Yong Hwan;Kim, Sung Zoo;Kim, Suhn Hee;Park, Woo Hyun
    • Molecules and Cells
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    • v.26 no.2
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    • pp.158-164
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    • 2008
  • Arsenic trioxide (ATO) affects many biological processes such as cell proliferation, apoptosis, differentiation and angiogenesis. L-buthionine sulfoximine (BSO) is an inhibitor of GSH synthesis. We tested whether ATO reduced the viability of lung cancer A549 cells in vitro, and investigated the in vitro effect of the combination of ATO and BSO on cell viability in relation to apoptosis and the cell cycle. ATO caused a dose-dependant decrease of viability of A549 cells with an $IC_{50}$ of more than $50{\mu}m$. Low doses of ATO or BSO ($1{\sim}10{\mu}m$) alone did not induce cell death. However, combined treatment depleted GSH content and induced apoptosis, loss of mitochondrial transmembrane potential (${\Delta}{\Psi}_m$) and cell cycle arrest in G2. Reactive oxygen species (ROS) increased or decreased depending on the concentration of ATO. In addition, BSO generally increased ROS in ATO-treated A549 cells. ROS levels were at least in part related to apoptosis in cells treated with ATO and/or BSO. In conclusion, we have demonstrated that A549 lung cells are very resistant to ATO, and that BSO synergizes with clinically achievable concentration of ATO. Our results suggest that combination treatment with ATO and BSO may be useful for treating lung cancer.