• BMB Reports
• /
• v.50 no.7
• /
• pp.345-354
• /
• 2017

Autophagy, a catabolic process necessary for the maintenance of intracellular homeostasis, has recently been the focus of numerous human diseases and conditions, such as aging, cancer, development, immunity, longevity, and neurodegeneration. However, the continued presence of autophagy is essential for cell survival and dysfunctional autophagy is thought to speed up the progression of neurodegeneration. The actual molecular mechanism behind the progression of dysfunctional autophagy is not yet fully understood. Emerging evidence suggests that basal autophagy is necessary for the removal of misfolded, aggregated proteins and damaged cellular organelles through lysosomal mediated degradation. Physiologically, neurodegenerative disorders are related to the accumulation of amyloid ${\beta}$ peptide and ${\alpha}-synuclein$ protein aggregation, as seen in patients with Alzheimer's disease and Parkinson's disease, respectively. Even though autophagy could impact several facets of human biology and disease, it generally functions as a clearance for toxic proteins in the brain, which contributes novel insight into the pathophysiological understanding of neurodegenerative disorders. In particular, several studies demonstrate that natural compounds or small molecule autophagy enhancer stimuli are essential in the clearance of amyloid ${\beta}$ and ${\alpha}-synuclein$ deposits. Therefore, this review briefly deliberates on the recent implications of autophagy in neurodegenerative disorder control, and emphasizes the opportunities and potential therapeutic application of applied autophagy.

• BMB Reports
• /
• v.51 no.1
• /
• pp.5-13
• /
• 2018

Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's, Huntington's, and prion diseases. The transglutaminase 2 (TG2) gene encodes a multifunctional enzyme, displaying four types of activity, such as transamidation, GTPase, protein disulfide isomerase, and protein kinase activities. Many studies demonstrated that the calcium-dependent transamidation activity of TG2 affects the formation of insoluble and toxic amyloid aggregates that mainly consisted of NDD-related proteins. So far, many important and NDD-related substrates of TG2 have been identified, including $amlyoid-{\beta}$, tau, ${\alpha}-synuclein$, mutant huntingtin, and ALS-linked trans-activation response (TAR) DNA-binding protein 43. Recently, the formation of toxic inclusions mediated by several TG2 substrates were efficiently inhibited by TG2 inhibitors. Therefore, the development of highly specific TG2 inhibitors would be an important tool in alleviating the progression of TG2-related brain disorders. In this review, the authors discuss recent advances in TG2 biochemistry, several mechanisms of molecular regulation and pleotropic signaling functions, and the presumed role of TG2 in the progression of many NDDs.

• Molecules and Cells
• /
• v.25 no.1
• /
• pp.1-6
• /
• 2008

Osteoarthritis (OA), one of the most common skeletal disorders characterized by cartilage degradation and osteophyte formation in joints, is induced by accumulated mechanical stress; however, little is known about the underlying molecular mechanism. Several experimental OA models in mice by producing instability in the knee joints have been developed to apply approaches from mouse genetics. Although proteinases like matrix metalloproteinases and aggrecanases have now been proven to be the principal initiators of OA progression, clinical trials of proteinase inhibitors have not been successful for the treatment, turning the interest of researchers to the upstream signals of proteinase induction. These signals include undegraded and fragmented matrix proteins like type II collagen or fibronection that affects chondrocytes through distinct receptors. Another signal is proinflammatory factors that are produced by chondrocytes and synovial cells; however, recent studies that used mouse OA models in knockout mice did not support that these factors have a role in the central contribution to OA development. Our mouse genetic approaches found that the induction of a transcriptional activator Runx2 in chondrocytes under mechanical stress contributes to the pathogenesis of OA through chondrocyte hypertrophy. In addition, chondrocyte apoptosis has recently been identified as being involved in OA progression. We hereby propose that these endochondral ossification signals may be important for the OA progression, suggesting that the related molecules can clinically be therapeutic targets of this disease.

• Genomics & Informatics
• /
• v.12 no.4
• /
• pp.156-164
• /
• 2014

Cancer is the most dreaded disease in human and also major health problem worldwide. Despite its high occurrence, the exact molecular mechanisms of the development and progression are not fully understood. The existing cancer therapy based on allopathic medicine is expensive, exhibits side effects; and may also alter the normal functioning of genes. Thus, a non-toxic and effective mode of treatment is needed to control cancer development and progression. Some medicinal plants offer a safe, effective and affordable remedy to control the cancer progression. Nimbolide, a limnoid derived from the neem (Azadirachta indica) leaves and flowers of neem, is widely used in traditional medical practices for treating various human diseases. Nimbolide exhibits several pharmacological effects among which its anticancer activity is the most promising. The previous studies carried out over the decades have shown that nimbolide inhibits cell proliferation and metastasis of cancer cells. This review highlights the current knowledge on the molecular targets that contribute to the observed anticancer activity of nimbolide related to induction of apoptosis and cell cycle arrest; and inhibition of signaling pathways related to cancer progression.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.15 no.1
• /
• pp.19-22
• /
• 2012

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract and characterized by relapsing and remitting episodes, with progression over time to complications of stricture, fistulas, or abscesses. The etiology is unknown, although the common opinion is that the disease arises from a disordered immune response to the gut contents in genetically predisposed individuals. Infliximab is a mouse-human chimeric antibody against tumor necrosis factor ${\alpha}$, and has proven to be effective in active Crohn's disease for both induction and maintenance therapy. Despite the growing experience with infliximab in Crohn's disease, optimal treatment strategies still need to be determined. The purpose of this review is to summarize the current knowledge on the use of infliximab in Crohn's disease and to discuss the yet-unsolved issues.

• 대한핵의학회:학술대회논문집
• /
• 2002.05a
• /
• pp.32-36
• /
• 2002

Lymphoma is a group of neoplastic disease of lymphoid tissues, which can be classified into categories of Hodgkin's disease and non-Hodgkin's lymphoma(NHL). Prognosis of lymphoma depends on the extent of disease(staging) especially in Hodgkin's disease, but also depends on the histologic make up in non-Hodgkin's lymphoma. Although non-Hodgkin's lymphoma is a neoplastic transformation of lymphoid cell it is a collection of disease with merphologically and immunologically diverse make up. Consequently the classification of NHL has changed frequently and evolved according to the progress of immunologic and molecular knowledge added to the original morphologic classification. Lymphoma is a disorder sensitive to chemotherapy which often leads to cure of the disease even in advanced stage, while many other patients die from the progression of disease. Therefore, better understanding in newer classification and sensitive imaging technique, such as PET, in lymphoma will likely lead to the improvement of survival rate.

• Korean Journal of Clinical Laboratory Science
• /
• v.51 no.1
• /
• pp.26-33
• /
• 2019

Recently, the rapid growth of the companion animal market has led to the development of animal disease diagnosis kits. Therefore, the utility of the introduction of biomarkers for the development of animal molecular diagnostics is being reevaluated. A good biomarker should be precise and reliable, distinguish between normal and diseased states, and differentiate between different diseases. Recently reported genetic markers, tumor markers (cell free DNA, circulating tumor cells, granzyme, and skin tumors), and others (brucellosis, programmed death recovery-1, symmetric dimethylarginine, periostin, and cysteinyl leukotrien) have been developed. The biomarkers are used for risk prediction or for the screening, diagnosis, and monitoring of disease progression. The most important criteria for related biomarkers are disease specificity. Many potential biomarkers have emerged from laboratory and test studies, but they have not been validated in independent or large-scale clinical studies. Candidate biomarkers evaluate disease associations, verify the effectiveness of biomarkers for early detection and disease progression, and incorporate them into humans and animals. In the future, it will be necessary to reevaluate the utility of well-structured biomarker-based research and study the development of kits that can be used in on-site tests in accordance with the trends introduced in the diagnosis of animal diseases.

• Journal of Cardiovascular Imaging
• /
• v.26 no.4
• /
• pp.229-237
• /
• 2018

BACKGROUND: Statins are thought to have little effect on the progression of aortic stenosis, but the data on their role in patients with aortic valve sclerosis (AVS) are limited and inconsistent. METHODS: We retrospectively analyzed 541 consecutive patients (214 men, age: $70{\pm}11$ years) with AVS. Each patient underwent two or more electrocardiography examinations at least 6 months apart at Kangwon National University Hospital from August 2010 to August 2015. AVS is defined as irregular thickening of the leaflets, focal increases in echogenicity and minimal elevation of the peak aortic valve velocity (> 1.5 and < 2 m/s). The progression rate of AVS was expressed as the increase in peak velocity per year (m/s/yr). RESULTS: The mean follow-up duration was $24.9{\pm}13.3$ months in the statin-treated group and $24.1{\pm}12.4$ months in the non-statin-treated group (p = 0.460). There were no differences between the statin-treated and non-statin-treated groups in mean age, gender or smoking status. Relative to the non-statin-treated group, a higher number of patients in the statin-treated group had hypertension, diabetes, ischemic heart disease, and stroke. The progression rate of AVS did not differ between the statin-treated and non-statin-treated groups ($0.012{\pm}0.340m/s/yr$ vs. $0.014{\pm}0.245m/s/yr$, p = 0.956). Multivariate analysis showed initial peak aortic jet velocity was significantly associated with AVS progression (${\beta}=0.153$, p = 0.009). CONCLUSIONS: Our study demonstrated that statins had no effect on the progression of AVS. However, well-designed studies are needed to define the prognosis and management of AVS.

• Korean Journal of Head & Neck Oncology
• /
• v.16 no.1
• /
• pp.58-63
• /
• 2000

Objectives: To demonstrate effective diagnostic method and proper management of recurrent thyroid cancer through to compare treatment and surveillance of $I^{131}$ scanning detected recurrence and clinically detected recurrence. Material and Methods: We retrospectively analyzed clinical information about 46 patients who has recurrent thyroid cancer of 298 patients who have been primarily operated due to thyroid cancer in PMC at the over 10 years between 1986 and 1995. We examine incidence of recurrence due to pathologic types, site of recurrence, disease free interval, detection method of recurrence, and also treatment and progression of recurrence. A patients in which the clinical examination was entirely negative and the $I^{131}$ scan demonstrated either a new area of $I^{131}$ uptake or an increased area of concentration, compared to the previous scan, was designated as a recurrence detected by $I^{131}$ scan only. Recurrences that were obviously by physical examination or chest x-ray, etc were considered clinically detected recurrence, regardless of the the results of the thyroid scan. Results: Mean of disease tree interval(DFI) is 36months. When mean DFI of $I^{131}$ scan detected recurrence is 28months, whereas mean DFI of clinically detected recurrence is 47months. In statiscal analysis, p-value is 0.043 as significantly. In progression of recurrent patient, NED is 28case, AWD is Sease, DOD is 13case. Among the 13case, scan detected recurrence is lease of 20 patients(5%), whereas clinically detected recurrence is l2case of 26 patient(46%). In statiscal analysis, p-value is 0.003 as significantly. Conclusion: Early detection of the recurrent thyroid cancer by $I^{131}$ scanning leads to good progress compare with detection by clinical examination. NED: No Evidence of Disease AWD : Alive With Disease DOD : Dead Of Disease DOC: Dead of Other Cause

• Korean Journal of Clinical Laboratory Science
• /
• v.47 no.4
• /
• pp.168-174
• /
• 2015

Rheumatoid arthritis (RA) is a chronic inflammatory disease, which is mainly characterized by disease of joints affected with synovial hyperplasia, pathological immune response, and progressive destruction; all of which represent an important social health problem. These provide new insights in its pathogenesis of rheumatoid arthritis diagnosis and disease progression in molecular changes. This review focuses on new serological and immunological markers which seem to be useful in early diagnosis and prognosis of rheumatoid arthritis. Therefore, such tests are widely conducted for serological biomarkers and the developments with such immunological factors to identify patients who are at risk for disease progression. This evidence of the disease based on laboratory medicine could provide the best outcome for patients. Finally, data from recent studies will help to refine the ultimate usefulness of this novel approach for early diagnosis, treatment, and helping clinicians to optimize therapy by using this approach.