• Title/Summary/Keyword: sclerosis

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Inhibition of VRK1 suppresses proliferation and migration of vascular smooth muscle cells and intima hyperplasia after injury via mTORC1/β-catenin axis

  • Sun, Xiongshan;Zhao, Weiwei;Wang, Qiang;Zhao, Jiaqi;Yang, Dachun;Yang, Yongjian
    • BMB Reports
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    • v.55 no.5
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    • pp.244-249
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    • 2022
  • Characterized by abnormal proliferation and migration of vascular smooth muscle cells (VSMCs), neointima hyperplasia is a hallmark of vascular restenosis after percutaneous vascular interventions. Vaccinia-related kinase 1 (VRK1) is a stress adaption-associated ser/thr protein kinase that can induce the proliferation of various types of cells. However, the role of VRK1 in the proliferation and migration of VSMCs and neointima hyperplasia after vascular injury remains unknown. We observed increased expression of VRK1 in VSMCs subjected to platelet-derived growth factor (PDGF)-BB by western blotting. Silencing VRK1 by shVrk1 reduced the number of Ki-67-positive VSMCs and attenuated the migration of VSMCs. Mechanistically, we found that relative expression levels of β-catenin and effectors of mTOR complex 1 (mTORC1) such as phospho (p)-mammalian target of rapamycin (mTOR), p-S6, and p-4EBP1 were decreased after silencing VRK1. Restoration of β-catenin expression by SKL2001 and re-activation of mTORC1 by Tuberous sclerosis 1 siRNA (siTsc1) both abolished shVrk1-mediated inhibitory effect on VSMC proliferation and migration. siTsc1 also rescued the reduced expression of β-catenin caused by VRK1 inhibition. Furthermore, mTORC1 re-activation failed to recover the attenuated proliferation and migration of VSMC resulting from shVrk1 after silencing β-catenin. We also found that the vascular expression of VRK1 was increased after injury. VRK1 inactivation in vivo inhibited vascular injury-induced neointima hyperplasia in a β-catenin-dependent manner. These results demonstrate that inhibition of VRK1 can suppress the proliferation and migration of VSMC and neointima hyperplasia after vascular injury via mTORC1/β-catenin pathway.

Histopathological evaluation of the lungs in experimental autoimmune encephalomyelitis

  • Sungmoo Hong;Jeongtae Kim;Kyungsook Jung;Meejung Ahn;Changjong Moon;Yoshihiro Nomura;Hiroshi Matsuda;Akane Tanaka;Hyohoon Jeong;Taekyun Shin
    • Journal of Veterinary Science
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    • v.25 no.3
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    • pp.35.1-35.13
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    • 2024
  • Importance: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by inflammation within the central nervous system. However, inflammation in non-neuronal tissues, including the lungs, has not been fully evaluated. Objective: This study evaluated the inflammatory response in lungs of EAE mice by immunohistochemistry and histochemistry. Methods: Eight adult C57BL/6 mice were injected with myelin oligodendrocyte glycoprotein35-55 to induce the EAE. Lungs and spinal cords were sampled from the experimental mice at the time of sacrifice and used for the western blotting, histochemistry, and immunohistochemistry. Results: Histopathological examination revealed inflammatory lesions in the lungs of EAE mice, characterized by infiltration of myeloperoxidase (MPO)- and galectin-3-positive cells, as determined by immunohistochemistry. Increased numbers of collagen fibers in the lungs of EAE mice were confirmed by histopathological analysis. Western blotting revealed significantly elevated level of osteopontin (OPN), cluster of differentiation 44 (CD44), MPO and galectin-3 in the lungs of EAE mice compared with normal controls (p < 0.05). Immunohistochemical analysis revealed both OPN and CD44 in ionized calcium-binding adapter molecule 1-positive macrophages within the lungs of EAE mice. Conclusions and Relevance: Taken together, these findings suggest that the increased OPN level in lungs of EAE mice led to inflammation; concurrent increases in proinflammatory factors (OPN and galectin-3) caused pulmonary impairment.

A Potential Risk of Radiation-Induced Cavernous Malformations Following Adjuvant Gamma Knife Radiosurgery for Mesial Temporal Lobe Epilepsy

  • Junhyung Kim;Joonho Byun;Do Heui Lee;Seok Ho Hong
    • Journal of Korean Neurosurgical Society
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    • v.67 no.4
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    • pp.458-466
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    • 2024
  • Objective : Several clinical studies have explored the feasibility and efficacy of radiosurgical treatment for mesial temporal lobe epilepsy, but the long-term safety of this treatment has not been fully characterized. This study aims to report and describe radiation-induced cavernous malformation as a delayed complication of radiosurgery in epilepsy patients. Methods : The series includes 20 patients with mesial temporal lobe epilepsy who underwent Gamma Knife radiosurgery (GKRS). The majority received a prescribed isodose of 24 Gy as an adjuvant treatment after anterior temporal lobectomy. Results : In this series, we identified radiation-induced cavernous malformation in three patients, resulting in a cumulative incidence of 18.4% (95% confidence interval, 6.3% to 47.0%) at an 8-year follow-up. These late sequelae of vascular malformation occurred between 6.9 and 7.6 years after GKRS, manifesting later than other delayed radiation-induced changes, such as radiation necrosis. Neurological symptoms attributed to intracranial hypertension were present in those three cases involving cavernous malformation. Of these, two cases, which initially exhibited an insufficient response to radiosurgery, ultimately demonstrated seizure remission following the successful microsurgical resection of the cavernous malformation. Conclusion : All things considered, the development of radiation-induced cavernous malformation is not uncommon in this population and should be acknowledged as a potential long-term complication. Microsurgical resection of cavernous malformation can be preferentially considered in cases where the initial seizure outcome after GKRS is unsatisfactory.

Therapeutic Effect of Crocin in Inflammatory Diseases (염증성 질환에 대한 Crocin의 치료 효과)

  • YoungHee Kim
    • Journal of Life Science
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    • v.34 no.2
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    • pp.138-144
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    • 2024
  • Crocin is a major carotenoid of the Gardenia jasminoides fruit and Crocus sativus stigma (saffron), which are used in various cuisines as flavoring and coloring agents, as well as in phytomedicine for the treatment of several disorders, including headache, fever, edema, fatty liver, viral hepatitis, respiratory disease, menstruation disorders, insomnia, and hypertension. Crocin (C44H64O24) is a chemical diester composed of the dicarboxylic acid crocetin and disaccharide gentiobiose. Many in vitro and in vivo studies have been conducted about the biological and pharmacological function and toxicity of crocin. Crocin has been revealed to have no genotoxicity and pathological manifestation. Crocin acts as an antioxidant, anti-cancer, memory enhancer, anxiolytic, antidepressant, aphrodisiac, anti-atherosclerotic, cardioprotector, and hepatoprotector. Here, an inclusive review of crocin is introduced based on previously explored studies referred to in the literature. Different studies have confirmed the protective role of crocin in the pathogenesis of inflammatory diseases, including inflammatory bowel diseases, gastritis, asthma, atherosclerosis, rheumatoid arthritis, multiple sclerosis, type 1 diabetes, Alzheimer's disease, Parkinson's disease, and depression. It is surmised that crocin suppresses inflammatory, antioxidant, and apoptotic processes through multiple mechanisms. Crocin is considered a safe and effective therapeutic choice for patients with inflammatory conditions, although more research investigating its mechanisms and results acquired in clinical trials are needed.

Korean Red Ginseng extract ameliorates demyelination by inhibiting infiltration and activation of immune cells in cuprizone-administrated mice

  • Min Jung Lee;Jong Hee Choi;Tae Woo Kwon;Hyo-Sung Jo;Yujeong Ha;Seung-Yeol Nah;Ik-Hyun Cho
    • Journal of Ginseng Research
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    • v.47 no.5
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    • pp.672-680
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    • 2023
  • Background: Korean Red Ginseng (KRG), the steamed root of Panax ginseng, has pharmacological activities for immunological and neurodegenerative disorders. But, the role of KRGE in multiple sclerosis (MS) remains unclear. Purpose: To determine whether KRG extract (KRGE) could inhibit demyelination in corpus callosum (CC) of cuprizone (CPZ)-induced murine model of MS Methods: Male adult mice were fed with a standard chow diet or a chow diet supplemented with 0.2% (w/w) CPZ ad libitum for six weeks to induce demyelination while were simultaneously administered with distilled water (DW) alone or KRGE-DW (0.004%, 0.02 and 0.1% of KRGE) by drinking. Results: Administration with KRGE-DW alleviated demyelination and oligodendrocyte degeneration associated with inhibition of infiltration and activation of resident microglia and monocyte-derived macrophages as well as downregulation of proinflammatory mediators in the CC of CPZ-fed mice. KRGE-DW also attenuated the level of infiltration of Th1 and Th17) cells, in line with inhibited Mrna expression of IFN-γ and IL-17, respectively, in the CC. These positive effects of KRGE-DW mitigated behavioral dysfunction based on elevated plus maze and the rotarod tests. Conclusion: The results strongly suggest that KRGE-DW may inhibit CPZ-induced demyelination due to its oligodendroglial protective and anti-inflammatory activities by inhibiting infiltration/activation of immune cells. Thus, KRGE might have potential in therapeutic intervention for MS.

Follow-up Study of Condylar Bone Changes using Cone Beam Computed Tomography in Patients with Osteoarthritis (측두하악장애 골관절염 환자에서 cone-beam CT를 이용한 관절면의 변화 추적 연구)

  • Ko, Chul-Hee;Kim, Byeong-Soo;Ko, Myung-Yun;Jeong, Sung-Hee;Ok, Soo-Min;Ahn, Yong-Woo
    • Journal of Oral Medicine and Pain
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    • v.37 no.1
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    • pp.33-45
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    • 2012
  • This study was designed to assess follow-up study of condylar bone changes using cone beam computed tomography in patients with osteoarthritis. The author performed clinical examination for osteoarthritis patients who visited Orofacial Pain Clinic, Department of Oral Medicine, Pusan National University Hospital. CBCT(Cone beam computed tomography) was taken for 228 joints in 114 subjects. After average 10 months, CBCT was retaken. A Oral medicine and Oral radiologist evaluated CBCT each other. Condyle bone changes were classified by no bone change, flattening, erosion, osteophyte and sclerosis. The obtained results were as follow. 1. The condylar bone changes of osteoarthritis in temporomandibular disorder were as follow: 1) The transitions of each types of condylar bone changes was maintained at the initial state of the majority. 2) The transition of erosion was distributed erosion, flattening, sclreosis, osteohyte in order. 3) The transition of flattening was distributed flattening, osteohyte, normal, sclreosis in order. 4) The transition of osteohyte was distributed osteohyte, erosion, sclreosis, flattening in order. 5) The transition of sclreosis was distributed sclreosis, osteohyte, erosion, normal in order. 2. The signs and symptoms according to transition of each types of condylar bone changes were as follow 1) In the transition of condylar bone changes from erosin to erosion, pain, noise, LOM and MCO had symptomatic improvement. In the transition of condylar bone changes from erosin to flattening, pain, LOM, MCO had symptomatic improvement. In the transition of condylar bone changes from erosin to no bony change, pain, noise, LOM had symptomatic improvement. In the transition of condylar bone changes from erosion to flattening than the maintenance of eosion, MCO had symptomatic improvement. 2) In the transition of condylar bone changes from flattening to flattening, pain, noise and MCO had symptomatic improvement. In the transition of condylar bone changes from flattening to sclerosis, LOM had symptomatic improvement. 3) In the transition of condylar bone changes from osteophyte to osteophyte, pain, LOM and MCO had symptomatic improvement.

Clinicopathologic features and prognosis of childhood IgA nephropathy (소아 IgA 신병증의 임상병리학적 양상과 예후)

  • Woo, Sung Il;Bae, Keun Wook;Lee, Joo Hoon;Park, Young Seo;Cho, Yong Mee
    • Clinical and Experimental Pediatrics
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    • v.50 no.2
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    • pp.170-177
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    • 2007
  • Purpose : Clinicopathological features were investigated to clarify the outcome and prognostic indicators for patients with IgA nephropathy in Korean children. Methods : We reviewed the outcomes of 61 patients in whom IgA nephropathy was diagnosed before the age of 15 years from 1991 to 2005 and followed-up at least for one year. All patients were confirmed by renal biopsy. Results : After mean follow-up of 5.2 years from onset, 24 patients of 61 (39.3%) were in clinical remission at the last examination. Thirty patients (49.2%) had hematuria or mild proteinuria (<$1g/m^2/d$), five (8.2%) had severe proteinuria (${\geq}1g/m^2/d$), and two (3.3%) had chronic renal failure. By univariate analysis, initial presentation at onset and Haas classification were less concordant with outcome. Hypertension during follow-up, rather than hypertension at presentation, was significantly correlated with outcomes (P<0.01). Sixty percent of patients who had more than 20% of glomerular sclerosis or crescent progressed to severe proteinuria or chronic renal failure, as compared with 7.1% of those who did not (P<0.01). Conclusion : Prognosis of childhood IgA nephropathy had a relatively benign course during a mean follow-up of 5.2 years. Persistent hypertension during follow-up and more than 20% of glomerular sclerosis or crescent were strong predictors of a progressive course of IgA nephropathy. A new histologic classification according to characteristics of childhood IgA nephropathy must be established to assess prognosis. Further efforts should be made to understand the prognosis of IgA nephropathy through long-term follow-up.

OSTEOPETROSIS Tarda : CASE REPORT (만발형 골화석증에 대한 증례보고)

  • Kweon, Jong-Pil;Yang, Kyu-Ho
    • Journal of the korean academy of Pediatric Dentistry
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    • v.26 no.3
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    • pp.473-478
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    • 1999
  • Osteopetrosis is an uncommon hereditary bone condition characterized by a generalized symmetric increase in skeletal density and abnormalities of bone resorption remodeling. In 1904, the first case of generalized sclerosis of the skeleton was reported by $Albers-Sch\ddot{o}nberg$. Osteopetrosis is generally divided into two main type. The infantile(malignant, congenita) type is the most severe form of the disease; It is characterized by skeletal and hematologic abnormalities. The adult(benign, tarda) type which is usually diagnosed in the third or fourth decade of life is limited predominantly to skeletal anomalies and it carries a more favorable prognosis. The recently recognized intermediate form with its mild and variable clinical recessive trait. There is no reported gender or racial predilection. The characteristic feature of osteopetrosis which is an abscence of physiologic bone resorption results in accumulation of bone mass and mainfests skeletal disturbance. Dental finding of osteopetrosis includes delayed eruption, congenitally absent teeth, unerupted and malformed teeth, and enamel hypoplasia. Our report involves a patient with a chief complaint of tooth mobility and delayed eruption. After clinical and radiologic examination, this patient was referred to dept. of pediatrics under the suspicion of osteopetrosis and it was confirmed.

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A Study on Wine Selection Attributes by Wine Use Behavior - Focused on Wine Retail Shop Customers - (와인 이용 행태에 따른 와인 선택 속성에 관한 연구 - 와인 소매점 이용고객을 중심으로 -)

  • Jeon, Hyeon-Mo;Park, Mi-Young
    • Culinary science and hospitality research
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    • v.15 no.2
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    • pp.121-135
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    • 2009
  • The pattern of liquor consumers started to change as the well-being trend and great interest in health have risen for the last few years. In particular, consumption of wine is gradually increasing with the findings revealing that drinking proper amount of wine is good for preventing various adult diseases such as sclerosis of the arteries, heart disease and aging. Accordingly, this study aims at understanding the importance of wine buyers' choice attributes when buying and drinking wine in order to contribute to satisfying customers, popularizing wine and expanding its base. From December 1 to 31 in 2008, it made a survey on natives and weekly settled population living in Seoul area who had bought wine at a wine retail shop with literature and positive researches. It made an application of SPSS 12.0 to analyze the importance of wine buyers' choice attribution based on the demographical characteristics and use behavior with such analysis methods as the frequency analysis, the factor analysis, the reliability test, ANOVA and multiple regression. The results are summarized as follows. First, it showed that there are significant differences between buying and drinking wine by producing countries, buying places, prices, companions except for the number of drinking times, drinking places, and information sources. Second, it showed that wine buyers' choice attributes such as brand characteristics and effects on health have a positive effect on customer satisfaction.

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Increased expression of galectin-9 in experimental autoimmune encephalomyelitis (실험적 자가면역성 뇌척수염을 유도한 마우스에서 Galectin-9의 과발현)

  • Cho, Jinhee;Bing, So Jin;Kim, Areum;Yu, Hak Sun;Lim, Yoon-Kyu;Shin, Taekyun;Choi, Jonghee;Jee, Youngheun
    • Korean Journal of Veterinary Research
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    • v.54 no.4
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    • pp.209-218
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    • 2014
  • Experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), reflects pathophysiologic steps in MS such as the influence of T cells and antibodies reactive to the myelin sheath, and the cytotoxic effect of cytokines. Galectin-9 (Gal-9) is a member of animal lectins that plays an essential role in various biological functions. The expression of Gal-9 is significantly enhanced in MS lesions; however, its role in autoimmune disease has not been fully elucidated. To identify the role of Gal-9 in EAE, we measured changes in mRNA and protein expression of Gal-9 as EAE progressed. Expression increased with disease progression, with a sharp rise occurring at its peak. Gal-9 immunoreactivity was mainly expressed in astrocytes and microglia of the central nervous system (CNS) and macrophages of spleen. Flow cytometric analysis revealed that $Gal-9^+CD11b^+$ cells were dramatically increased in the spleen at the peak of disease. Increased expression of tumor necrosis factor (TNF)-R1 and p-Jun N-terminal kinase (JNK) was observed in the CNS of EAE mice, suggesting that TNF-R1 and p-JNK might be key regulators contributing to the expression of Gal-9 during EAE. These results suggest that identification of the relationship between Gal-9 and EAE progression is critical for better understanding Gal-9 biology in autoimmune disease.