• Title/Summary/Keyword: cause of disease and pathogenesis

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LJ-2698, an Adenosine A3 Receptor Antagonist, Alleviates Elastase-Induced Pulmonary Emphysema in Mice

  • Boo, Hye-Jin;Park, So Jung;Noh, Myungkyung;Min, Hye-Young;Jeong, Lak Shin;Lee, Ho-Young
    • Biomolecules & Therapeutics
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    • v.28 no.3
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    • pp.250-258
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    • 2020
  • Emphysema, a major component of chronic obstructive pulmonary disease (COPD), is a leading cause of human death worldwide. The progressive deterioration of lung function that occurs in the disease is caused by chronic inflammation of the airway and destruction of the lung parenchyma. Despite the main impact of inflammation on the pathogenesis of emphysema, current therapeutic regimens mainly offer symptomatic relief and preservation of lung function with little therapeutic impact. In the present study, we aimed to discover novel therapeutics that suppress the pathogenesis of emphysema. Here, we show that LJ-2698, a novel and highly selective antagonist of the adenosine A3 receptor, a G protein-coupled receptor involved in various inflammatory diseases, significantly reversed the elastase-induced destructive changes in murine lungs. We found that LJ-2698 significantly prevented elastase-induced airspace enlargement, resulting in restoration of pulmonary function without causing any obvious changes in body weight in mice. LJ-2698 was found to inhibit matrix metalloproteinase activity and pulmonary cell apoptosis in the murine lung. LJ-2698 treatment induced increases in anti-inflammatory cytokines in macrophages at doses that displayed no significant cytotoxicity in normal cell lines derived from various organs. Treatment with LJ-2698 significantly increased the number of anti-inflammatory M2 macrophages in the lungs. These results implicate the adenosine A3 receptor in the pathogenesis of emphysema. Our findings also demonstrate the potential of LJ-2698 as a novel therapeutic/preventive agent in suppressing disease development with limited toxicity.

Immune thrombocytopenia associated with sarcoidosis (면역성혈소판감소증을 동반한 사르코이드증)

  • Jeong, Da Eun;Kim, Min Kyoung;Koh, Sung Ae;Lee, Kyoung Hee;Choi, Joon Hyuk;Hong, Young Hoon;Cho, Jae Ho;Goo, Eun Ju;Hyun, Myung Soo
    • Journal of Yeungnam Medical Science
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    • v.32 no.1
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    • pp.26-30
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    • 2015
  • Sarcoidosis is a systemic disease of unknown cause involving multiple organs and is characterized by noncaseating granuloma. Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased peripheral platelet destruction due to the presence of an antibody to the platelet and abnormal platelet production. There is no known pathogenesis that occurs concurrently with ITP and sarcoidosis. However, considering together of 2 known pathogenesis, abnormal immune response triggers either ITP or sarcoidosis. The disease that develops first stimulates secondary disease. After development of secondary disease, they stimulate each other. A few cases of ITP associated with sarcoidosis are well documented in English; however, the disease has rarely been reported in Korea. Here, we report on a case of ITP with sarcoidosis in a 29-year-old man. He suffered from easy bruising. The chest X-ray and the contrast-enhanced computed tomography scan showed bihilar lymphadenopathy and reticulonodular infiltrates. Bone marrow study and fluoroscopy-guided percutaneous needle biopsy were performed and the patient was diagnosed with sarcoidosis and ITP. He was put on 400 mg/kg of intravenous immunoglobulin for 5 days and administered oral steroids and further follow-up will be carried out. He has shown a good response without significant bleeding event. However, administration of more oral steroid and additional follow-up is required than for single disease, whether sarcoidosis or ITP.

Pancreatic Cancer: Pathogenesis and Diagnosis

  • Goral, Vedat
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5619-5624
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    • 2015
  • Pancreatic cancer is a fatal malignancies which is predominantly seen in men and at advanced age (40-85 years) and has an aggressive course. Its frequency is gradually increasing over the past years. It accounts for 2% of all cancers and 5% of cancer-related deaths. Pancreatic cancer takes the first place among asymptomatic cancers. Ninety percent of cases are adenocarcinomas. Ten percent of the patients have a familial disposition. The disease is very difficult to detect as it has no early signs and spreads rapidly to surrounding organs is one of the most deadly types of cancer. Pancreatic cancer may result from hereditary germline or somatic acquired mutations in cancer-related genes and mutations also cause cancer progression and metastasis.

Pathogenesis of Minimal Change Nephrotic Syndrome: A Review of the Underlying Molecular Mechanisms

  • Yang, Eun Mi
    • Childhood Kidney Diseases
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    • v.23 no.1
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    • pp.1-6
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    • 2019
  • Nephrotic syndrome (NS) is the most common glomerular disorder in childhood, and a vast majority of cases are idiopathic. The precise cause of this common childhood disease is not fully elucidated despite significant advancements in our understanding of podocyte biology. Idiopathic NS has been considered "a disorder of T-cell function" mediated by a circulating factor that alters podocyte function resulting in massive proteinuria since the last four decades. Several circulatory factors released from T-cells are considered to be involved in pathophysiology of NS; however, a single presumptive factor has not been defined yet. Extended evidence obtained by advances in the pathobiology of podocytes has implicated podocytes as critical regulator of glomerular protein filtration and podocytopathy. The candidate molecules as pathological mediators of steroid-dependent NS are CD80 (also known as B7-1), hemopexin, and angiopoietin-like 4. The "two-hit" hypothesis proposes that the expression of CD80 on podocytes and ineffective inhibition of podocyte CD80 due to regulatory T-cell dysfunction or impaired autoregulation by podocytes results in NS. Recent studies suggest that not only T cells but also other immune cells and podocytes are involved in the pathogenesis of MCNS.

Exposure to Phthalate Esters and the Risk of Endometriosis

  • Kim, Ju Hee;Kim, Sung Hoon
    • Development and Reproduction
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    • v.24 no.2
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    • pp.71-78
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    • 2020
  • Endometriosis is a common gynecologic disease, worldwide, whose true prevalence is uncertain because it is a difficult disease to diagnose. Endometriosis is a common cause of chronic pelvic pain, dysmenorrhea, and infertility, and is also associated with ovarian cancer. Although the risk factors for endometriosis are unclear, there is increasing evidence that exposure to environmental contaminants, especially phthalates, could affect the pathogenesis of endometriosis. Phthalates are industrial chemicals, used to make flexible plastics, and are present in numerous common plastic products, including medical devices and materials. Several in vitro studies have suggested a positive association between exposure to phthalate, or phthalate metabolites, and the risk of endometriosis. Since the 2000s, studies based on human plasma and urinary concentrations of various phthalate metabolites have been published, but there are still limitations to our understanding of the pathophysiology of phthalates and endometriosis. This report aims to review the current state of knowledge about a possible role of phthalates in the pathogenesis of endometriosis based on cell culture, animal models, and human data.

Protective Effects of Ramie (Boehmeria nivea) against Oxidative Stress in C6 Glial Cells

  • Wang, Xiaoning;Cho, Sunghun;Kim, Ho Bang;Jung, Yong-Su;Cho, Eun Ju;Lee, Sanghyun
    • Korean Journal of Plant Resources
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    • v.28 no.6
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    • pp.675-681
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    • 2015
  • β amyloid protein (Aβ) plays a critical role in the pathogenesis of Alzheimer's disease (AD) and possibly in Aβ-induced mitochondrial dysfunction and oxidative stress. Aβ can directly cause reactive oxygen species (ROS) production. Overproduction of ROS is considered to be involved in the pathogenesis of neurodegeneration of AD. Here, we investigated 9 kinds of ramie (Boehmeria nivea, (L.) Gaud., BN; hereafter denoted as BN) for their protective action against oxidative stress in a cellular system using C6 glial cells. We observed loss of cell viability and high levels of ROS generation after treatment with hydrogen peroxide (H2O2) and Aβ25-35. However, treatments with BN extracts led to an increase in cell viability and decrease in ROS production induced by H2O2 and Aβ25-35. In particular, the extracts of BN-01 (seobang variety from Seocheon) and BN-09 (local variety from Yeonggwang) showed excellent anti-oxidative properties. This indicates that BN extracts could prevent neurodegeneration by reducing oxidative stress in cells.

Involvement of Hepatic Innate Immunity in Alcoholic Liver Disease

  • Byun, Jin-Seok;Jeong, Won-Il
    • IMMUNE NETWORK
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    • v.10 no.6
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    • pp.181-187
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    • 2010
  • Excessive alcohol consumption is one of the critical causative factors leading to alcoholic liver disease (ALD). ALD is characterized by a wide spectrum of liver damage, ranging from simple uncomplicated liver steatosis (fatty liver) to steatohepatitis and liver fibrosis/cirrhosis. It has been believed that the obvious underlying cause for ALD is due to hepatocyte death induced by alcohol itself. However, recent sparkling studies have shown that diverse immune responses contribute to ALD because liver is enriched with numerous immune cells. Especially, a line of evidence has suggested that innate immune cells such as Kupffer cells and natural killer (NK)/NKT cells are significantly involved in the pathogenesis of ALD via production of pro-inflammatory cytokines and other mediators. Indeed, more interestingly, hepatic stellate cells (HSCs), known as a major cell inducing liver steatosis and fibrosis, can be killed by liver NK cells, which could be suppressed by chronic alcohol consumption. In this review, with the view of liver as predominant innate immune organ, we describe the pathogenesis of ALD in which what roles of innate immune cells are and how they are interacting with HSCs.

Association between dementia and oral health (치매와 구강 건강의 관계)

  • Kang, Kyung Lhi
    • The Journal of the Korean dental association
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    • v.56 no.4
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    • pp.218-230
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    • 2018
  • According to the burst of aged people, researchers have focused on aging-related diseases. Cognitive impairment including Alzheimer's disease (AD), one of the representative diseases related to aging, has no treatment option until now. Recently, it has been revealed that systemic inflammation plays a fundamental role in the pathogenesis of AD. Previous studies have suggested the association between poor oral health and cognitive impairment. Poor oral health can cause dental caries, chronic periodontitis, multiple tooth loss, and poor chewing ability, etc. Especially, periodontitis is a well-known chronic inflammatory disease and affects cognitive impairment directly and indirectly by inflammatory products mediators. Therefore, reduction of pathogenic microbial burden and inflammatory products by treating periodontitis can be a therapeutic modality to prevent cognitive impairment or to slow down the progression of it. Future studies are necessary to elucidate the causal relations and plausible mechanisms between poor oral health and cognitive impairment.

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Update on pertussis and pertussis immunization

  • Hong, Jung-Yun
    • Clinical and Experimental Pediatrics
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    • v.53 no.5
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    • pp.629-633
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    • 2010
  • Pertussis is a highly contagious respiratory tract disease caused by $Bordetella$ $pertussis$ infection. The clinical manifestation of this infection can be severe enough to cause death. Although pertussis has been supposed to be a vaccine-preventable disease ever since the widespread vaccination of children against pertussis was started, since the 1990s, cases of pertussis and related fatalities are on the rise, especially in countries with high vaccination coverage. In Korea, there have been no deaths due to pertussis since 1990, and the vaccination rate continues to be approximately 94%. However, the number of pertussis cases reported to the Korea Center for Disease Control and Prevention has tended to increase in the 2000s, and in 2009, there was an obvious increase in the number of pertussis cases reported. This review aims to present the latest information about the pathogenesis, diagnosis, treatment, and prevention of pertussis.

Co-Infection with Cytomegalovirus and Helicobacter pylori in a Child with $M\acute{e}n\acute{e}$trier's Disease

  • Yoo, Yangho;Lee, Yoon;Lee, Yoo Min;Choe, Yon Ho
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.16 no.2
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    • pp.123-126
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    • 2013
  • $M\acute{e}n\acute{e}$trier's disease is a rare protein-losing gastropathy characterized by hypertrophic gastric fold, foveolar hyperplasia, and hypoproteinemia with resulting peripheral edema. It is clinically evident as nonspecific gastrointestinal symptoms, including abdominal discomfort, nausea and vomiting, abdominal pain, weight loss, diarrhea, and edema. Pediatric $M\acute{e}n\acute{e}$trier's disease usually has an insidious onset and progressive, chronic clinical course and it spontaneously resolves in weeks or months. The pathogenesis of $M\acute{e}n\acute{e}$trier's disease is not clearly understood. $M\acute{e}n\acute{e}$trier's disease is thought to be associated with some gastric infections. But the cause of $M\acute{e}n\acute{e}$trier's disease is unknown, an association with cytomegalovirus (CMV) and Helicobacter pylori has been suggested. In Korea, We present the first a case of pediatric $M\acute{e}n\acute{e}$trier's disease with positive evidence of CMV and H. pylori.