• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.479-484
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• 2015

NOD2 (nucleotide-binding and oligomerization domain 2) was initially reported as a susceptibility gene for Crohn's disease, with several studies focused on elucidating its molecular mechanism in the progression of Crohn's disease. We now know that NOD2 is an intracellular bacterial sensing receptor, and that MDP-mediated NOD2 activation drives inflammatory signaling. Various mutations in NOD2 have been reported, with NOD2 loss of function being associated with the development of Crohn's disease and other autoimmune diseases. These results suggest that NOD2 not only has an immune stimulatory function, but also an immune regulatory function. Atherosclerosis is a chronic inflammatory disease of the arterial wall; its pathologic progression is highly dependent on the immune balance. This immune balance is regulated by infiltrating monocytes and macrophages, both of which express NOD2. These findings indicate a potential role of NOD2 in atherosclerosis. The purpose of this review is to outline the known roles of NOD2 signaling in the pathogenesis of atherosclerosis.

• Food Science of Animal Resources
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• v.31 no.2
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• pp.147-157
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• 2011

Mycobacterium avium paratuberculosis (MAP), the cause of Johne's disease in animals, may be a causative agent of Crohn's disease (CD) in humans, but the evidence supporting this claim is controversial. Milk, meat, and water could be potential sources of MAP transmission to humans. Thus, if the link between MAP and Crohn's disease is substantiated, the fact that MAP has been detected in retail foods could be a public health concern. The purpose of the present study was to review the link between MAP and CD, the prevalence of MAP in foods, heat inactivation, control of MAP during food processing, and detection methods for MAP. Although MAP positive rates in retail milk in nine countries ranged from 0 to 2.9% by the culture method and from 4.5 to 15.5% by PCR, high temperature short time pasteurization can effectively control MAP. The effectiveness of pasteurization to inactivate MAP depends on the initial concentration of the MAP in raw milk. Development of highly sensitive and specific rapid detection methods for MAP may enhance investigation into the relationship between MAP and CD, the prevention of the spread of MAP, and problem-solving related to food safety. Collaboration and efforts by government agencies, the dairy industry, farmers, veterinarians, and scientists will be required to reduce and prevent MAP in food.

• Biomedical Science Letters
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• v.26 no.1
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• pp.47-50
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• 2020

Recently, decades of robust researches on degenerative brain disorder have been highlighted on the interactive connection of gut and brain. In terms of inflammatory cytokine production, others have shown that Nucleotide-Binding Oligomerization Domain Containing 2 (NOD2) is involved with Leucine-Rich Repeat Kinase 2 (LRRK2). HEK293T cells were transiently co-transfected with Myc-tagged LRRK2 and Flag-tagged NOD2 and then followed by co-immunoprecipitation assay. In this study, we provide the novel finding of physical protein-protein interaction between NOD2 and LRRK2. G2019S variant has shown stronger interactions against NOD2 than those of wild type LRRK2. In an axis of NOD2-LRRK2 communication, it is believed to pave a new way in the understanding of the bidirectional molecular mechanism of brain disorder, including Parkinson's disease into gut inflammatory disease, including Crohn's disease.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.6
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• pp.564-570
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• 2021

Perianal fistulizing diseases, namely perianal fistulas and/or abscesses, are well-known complications of Crohn's disease (CD). These are known to develop more frequently in Asian children with CD, especially in the early stages of the disease course. Approximately half of the pediatric CD cases in Korea present with perianal fistulizing diseases at diagnosis. We report a rare case of a 12-year-old boy with CD with an incidental discovery of a perianal abscess on pelvic magnetic resonance imaging during CD diagnosis. No symptoms or signs of perianal fistulizing disease were identified. The early diagnosis of the perianal abscess enabled timely and effective treatment. Considering the high incidence of concomitant perianal CD in Korean children at diagnosis, perianal imaging may be useful and should be considered during diagnostic evaluation, even in patients with no subjective or objective findings indicating perianal CD.

• The Journal of Pediatrics of Korean Medicine
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• v.35 no.4
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• pp.56-74
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• 2021

Objectives The purpose of this study is to analyze the trend of herbal medicine treatment, treatment's effect and stability for Crohn's disease by reviewing clinical studies published over the past 5 years. Methods 22 articles which were published from 2017 to August, 2021 were obtained from the ScienceON, Research information sharing service (RISS), Koreanstudies Information Service System (KISS), Oriental medicine advanced searching integrated system (OASIS), China national knowledge infrastructure (CNKI), Pubmed. We analyzed the literature in regards to the treatment methods and results. Results There were 6 case reports, 1 controlled clinical trial, and 15 randomized controlled trial and in most cases, herbal medicines and Western medicines were administered in combination. The pathology of damp-heat due to spleen deficiency was the most common, and Sijunzi-tang and Shenling Baishu san were the most commonly used. As a result of the treatment, it was found that the combined administration of the herbal medicine and the Western medicine was more effective than the administration of the Western medicine alone. Conclusions Herbal treatment of Crohn's disease induced high cure rate safely than when only western treatment was applied. Future studies on safety and studies that can suggest specific guidelines for the combined administration of western and herbal medicines are needed.

• Childhood Kidney Diseases
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• v.22 no.2
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• pp.81-85
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• 2018

Amyloidosis is a rare disease that results from the deposition of extracellular protein in various body tissues, causing progressive organ dysfunction. Secondary renal amyloidosis is a rare but serious complication of chronic inflammatory bowel disease, particularly in patients with Crohn's disease or ulcerative colitis. We report a case of secondary renal amyloidosis in a pediatric patient who reported a 16-year history of "very early onset inflammatory bowel disease". Intensive treatment including repeated infliximab infusions improved clinical parameters of inflammatory bowel disease, although renal dysfunction showed progression. Amyloidosis should be considered in patients with IBD, particularly if they suffered disease progression.

• Korean Journal of Acupuncture
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• v.25 no.2
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• pp.159-177
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• 2008

Objectives : Crohn's disease is a severe chronic inflammation that is treated mainly by immunosuppression, which often has serious side effects. There is need to develop new therapeutic methods or drugs that have few side effects in order to treat this disease. Acupuncture with Moxi-tar at Cheonchu (ST25) has anti-inflammatory properties, but the mechanism of its anti-inflammatory actions is unclear. We investigated the protective effects and speculated the mechanisms of acupuncture with Moxi-tar at ST25 on trinitrobenzene sulfonic acid (TNBS) induced colitis in mice which is a well known Crohn's disease animal model. Methods : 5 % TNBS was treated at day 1 and day 7 into rectum of mice. To investigate therapeutic effects of acupuncture with Moxi-tar at ST25, acupuncture was carried out on day 3, and day 6. For the data analysis, we observed macroscopic and microscopic findings of the colon. Weight and width of the colon, degree of damage, changes of body weight, and myeloperoxygenase (MPO) activity were checked. For analysing protein expression, we carried out immunohistochemical staining and Western blot. For analysing mRNA expression, RT-PCR was carried out. Results : TNBS induced damages on the colon of mice, while acupuncture of Moxi-tar at ST25 suppressed TNBS mediated damages similar to those on the colons of mice in the control (not treated with TNBS) group. The average body weight of TNBS treated mice (77.4%) was decreased compared with that of the control mice (105%), and acupuncture with Moxi-tar at ST25 suppressed the loss of body weight caused by TNBS (from 77.4% to 95.3%). TNBS induced infiltration of immune cells in all layers of the colon while acupuncture with Moxi-tar at ST25 suppressed infiltration of immune cells caused by TNBS. Furthermore, acupunctured with Moxi-tar at ST25 suppressed macro-, micro- colonic damages caused by TNBS. Acupunctured with Moxi-tar at ST25 dramatically improved the clinical and histopathological symptoms such as the increase in weight of the distal colon and the MPO activity in TNBS-induced colitis. Acupuncture with Moxi-tar at ST25 down-regulated the nuclear transcription factor kappa B ($NF-{\kappa}B$) activity and suppressed tumor necrosis factor-a (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-1${\beta}$), and intracellular adhesion molecule-1 (ICAM-1) expressions caused by TNBS. Conclusions : Acupuncture with Moxi-tar at ST25 helps recovery from the TNBS-induced colonic damage by down-regulation of $NF-{\kappa}B$ activity and suppressing of TNF-${\alpha}$, IL-1${\beta}$, and ICAM-1 expressions. This may be an important method for the treatment of Crohn's disease.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.22 no.4
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• pp.358-368
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• 2019

Purpose: Pediatric Crohn's disease (CD) is directly related to growth and has a high probability of requiring surgical intervention(s); therefore, more active treatment for CD is required for children. This study investigated the impact of biologics on growth and disease course associated with surgery. Methods: This was a retrospective cohort study involving patients diagnosed with CD at the Seoul National University Children's Hospital (Seoul, Korea) between January 2006 and October 2017. The aim was to determine the characteristics of pediatric patients with CD and whether biologics affected growth and the surgical disease course. Results: Among patients who underwent surgery for CD, the mean number of operations per patient was 1.89. The mean time from initial diagnosis to surgery was 19.3 months. The most common procedure was fistulectomy (34%), followed by incision and drainage (25%). In all patients, the use of biologics increased the height (p=0.002) and body mass index (BMI) (p=0.005). Among patients who underwent surgery, height (p=0.004) and BMI (p=0.048) were increased in the group using biologics. Patients who used biologics exhibited a low operation rate only within 2 years after diagnosis, with no differences thereafter (p=0.027). Conclusion: Although biologics could not mitigate the operation rate in pediatric patients who underwent surgery for CD, biological therapy delayed disease progression within 2 years of disease onset. Additionally, biologics conferred growth and BMI benefits in this window period. Therefore, it may be helpful to use biologics for optimal growth in pediatric patients with a high probability of undergoing future surgery.

• Korean Journal of Acupuncture
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• v.37 no.3
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• pp.183-190
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• 2020

This case report details two remissions at onset and relapse after 4 years each with Korean herbal medicine treatment in a 33-year-old male patient diagnosed as Crohn's disease (CD) by clinical and colonoscopic examination. He presented bloody diarrhea and severe abdominal pain, and his symptoms were persistent even with usual Western medications, so he was offered surgery and biologics. He was then given Sayeok-Tang for 8 months and remission was induced. Four years later he had a relapse and this time he was given Banha-Sasim-Tang, and Baekduong-Ga-Gamcho-Agyo-Tang, based on pattern changes with intense symptom monitoring. Clinical and endoscopic remission was confirmed after 4 months of herbal medicine treatment and no adverse events were reported. This case report shows that individualized Korean herbal medicine treatment has the potential for induction of remission of CD and further research is warranted.

• BMB Reports
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• v.48 no.5
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• pp.243-248
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• 2015

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). As such, functions and dysfunctions of LRRK2 in PD have been the subject of extensive investigation. In addition to PD, increasing evidence is suggesting that LRRK2 is associated with a wide range of diseases. Genome-wide association studies have implicated LRRK2 in Crohn's disease (CD) and leprosy, and the carriers with pathogenic mutations of LRRK2 show increased risk to develop particular types of cancer. LRRK2 mutations are rarely found in Alzheimer's disease (AD), but LRRK2 might play a part in tauopathies. The association of LRRK2 with the pathogenesis of apparently unrelated diseases remains enigmatic, but it might be related to the yet unknown diverse functions of LRRK2. Here, we reviewed current knowledge on the link between LRRK2 and several diseases, including PD, AD, CD, leprosy, and cancer, and discussed the possibility of targeting LRRK2 in such diseases. [BMB Reports 2015; 48(5): 243-248]