• 한국운동역학회지
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• 제30권1호
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• pp.83-91
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• 2020

Objective: The study aimed to develop a functional performance index that evaluates the functional performance of Parkinson's patients, i.e., to integrate biomechanical measurements of walking, balance, muscle strength and tremor, and to use multiple linear regression with stepwise methods to identify the most suitable predictors for the progression of disease. Method: A total of 60 subjects were tested for sub-variables of four factors: walking, balance, isometric strength and hand tremors. Potential independet variables were extracted through correlation analysis of the sub-variables and dependent variables, Hoehn & Yahr scale. And then, a stepwise multiple regression analysis using the potential independent variables was performed to identify predictor of Hoehn & Yahr scale. Results: First, the results of the study showed that physical composition and gait had a relatively more correlated with the progression of the disease, compared to balance and hand tremor. Second, Parkinson's functional performance is characterized by dynamic pattern of walking, such as foot clearance and turning angle (TA) of walking, and a high-explained regression model is completed. Conclusion: The study emphasized the importance of walking variables and body composition in minor pathological features compared to Parkinson's patient's balancing ability and hand tremor. Specifically, it revealed that dynamic walking patterns functionally characterize patients. The results are worth considering when assessing functional performance related to the progression of the disease at the site.

• Laboraroty Animal Research
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• 제34권4호
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• pp.133-139
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• 2018

Nonalcoholic steatohepatitis (NASH) is becoming common chronic liver disease because of the increasing global prevalence of obesity and consequently Nonalcoholic fatty liver disease (NAFLD). However, the mechanism for progression of NAFLD to NASH and then cirrhosis is not completely understood, yet. The triggering of these hepatic diseases is thought from hepatocyte injury caused by over-accumulated lipid toxicity. Injured hepatocytes release damage-associated molecular patterns (DAMPs), which can stimulate the Kupffer cells (KCs), liver-resident macrophages, to release pro-inflammatory cytokines and chemokines, and recruit monocyte-derived macrophages (MDMs). The increased activation of KCs and recruitment of MDMs accelerate the progression of NAFLD to NASH and cirrhosis. Therefore, characterization for activation of hepatic macrophages, both KCs and MDMs, is a baseline to figure out the progression of hepatic diseases. The purpose of this review is to discuss the current understanding of mechanisms of NAFLD and NASH, mainly focusing on characterization and function of hepatic macrophages and suggests the regulators of hepatic macrophages as the therapeutic target in hepatic diseases.

• Molecules and Cells
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• 제45권5호
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• pp.343-352
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• 2022

The advent of the assay for transposase-accessible chromatin using sequencing (ATAC-seq) has shown great potential as a leading method for analyzing the genome-wide profiling of chromatin accessibility. A comprehensive reference to the ATAC-seq dataset for disease progression is important for understanding the regulatory specificity caused by genetic or epigenetic changes. In this study, we present a genome-wide chromatin accessibility profile of 44 liver samples spanning the full histological spectrum of nonalcoholic fatty liver disease (NAFLD). We analyzed the ATAC-seq signal enrichment, fragment size distribution, and correlation coefficients according to the histological severity of NAFLD (healthy control vs steatosis vs fibrotic nonalcoholic steatohepatitis), demonstrating the high quality of the dataset. Consequently, 112,303 merged regions (genomic regions containing one or multiple overlapping peak regions) were identified. Additionally, we found differentially accessible regions (DARs) and performed transcription factor binding motif enrichment analysis and de novo motif analysis to determine new biomarker candidates. These data revealed the gene-regulatory interactions and noncoding factors that can affect NAFLD progression. In summary, our study provides a valuable resource for the human epigenome by applying an advanced approach to facilitate diagnosis and treatment by understanding the non-coding genome of NAFLD.

• Biomolecules & Therapeutics
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• 제32권3호
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• pp.291-300
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• 2024

Autosomal dominant polycystic kidney disease (ADPKD), a congenital genetic disorder, is a notable contributor to the prevalence of chronic kidney disease worldwide. Despite the absence of a complete cure, ongoing research aims for early diagnosis and treatment. Although agents such as tolvaptan and mTOR inhibitors have been utilized, their effectiveness in managing the disease during its initial phase has certain limitations. This review aimed to explore new targets for the early diagnosis and treatment of ADPKD, considering ongoing developments. We particularly focus on cell polarity, which is a key factor that influences the process and pace of cyst formation. In addition, we aimed to identify agents or treatments that can prevent or impede the progression of renal fibrosis, ultimately slowing its trajectory toward end-stage renal disease. Recent advances in slowing ADPKD progression have been examined, and potential therapeutic approaches targeting multiple pathways have been introduced. This comprehensive review discusses innovative strategies to address the challenges of ADPKD and provides valuable insights into potential avenues for its prevention and treatment.

• Journal of Ginseng Research
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• 제43권2호
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• pp.312-318
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• 2019

Background: To date, no study has described disease progression in Asian patients infected with HIV-1 subtype D. Methods: To determine whether the disease progression differs in patients infected with subtypes D and B prior to starting combination antiretroviral therapy, the annual decline (AD) in $CD^{4+}$ T cell counts over $96{\pm}59months$ was retrospectively analyzed in 163 patients and compared in subtypes D and B based on the nef gene. Results: $CD^{4+}$ T cell AD was significantly higher in the six subtype D-infected patients than in the 157 subtype B-infected patients irrespective of Korean Red Ginseng (KRG) treatment (p < 0.001). Of these, two subtype D-infected patients and 116 subtype B-infected patients had taken KRG. AD was significantly lower in patient in the KRG-treated group than in those in the $KRG-na{\ddot{i}}ve$ group irrespective of subtype (p < 0.05). To control for the effect of KRG, patients not treated with KRG were analyzed, with AD found to be significantly greater in subtype D-infected patients than in subtype B-infected patients (p < 0.01). KRG treatment had a greater effect on AD in subtype D-infected patients than in subtype B-infected patients (4.5-fold vs. 1.6-fold). Mortality rates were significantly higher in both the 45 $KRG-na{\ddot{i}}ve$ (p < 0.001) and all 163 (p < 0.01) patients infected with subtype D than subtype B. Conclusion: Subtype D infection is associated with a >2-fold higher risk of death and a 2.9-fold greater rate of progression than subtype B, regardless of KRG treatment.

• Childhood Kidney Diseases
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• 제22권2호
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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.

• Journal of Korean Neurosurgical Society
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• 제55권1호
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• pp.5-11
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• 2014

Objective : We evaluated pseudoprogression (PsPD) following radiation therapy combined with concurrent temozolomide (TMZ), and we assessed pseudoresponse following anti-angiogenic therapy for patients with recurrent disease using the Response Assessment of the Neuro-Oncology Working Group. Methods : Patients who were pathologically confirmed as having high-grade glioma received radiotherapy with concurrent TMZ followed by adjuvant TMZ. Bevacizumab (Avastin) with CPT-11 were used as a salvage option for cases of radiologic progression. Magnetic resonance imaging (MRI) was routinely performed 1 month after concurrent radiochemotherapy (CRT) and every 3 months thereafter. For cases treated with the bevacizumab-containing regimen for progressive disease, MRI was performed every 2 months. Results : Of 55 patients, 21 (38%) showed radiologic progression within 4 weeks after CRT. Of these patients, 16 (29%) showed progression at second post-CRT MRI (etPD) and five (9%) showed improvement (PsPD). Seven of thirty-four initially non-progressed patients showed progression at the second post-CRT MRI (ltPD). No difference in survival was observed between the etPD and ltPD groups (p=0.595). Five (50%) of ten patients showed a radiological response after salvage bevacizumab therapy. Four of those patients exhibited rapid progression immediately after discontinuation of the drug (drug holiday). Conclusion : Twelve weeks following treatment could be the optimal timing to determine PsPD or true progression. MRI with gadolinium enhancement alone is not sufficient to characterize tumor response or growth. Clinical correlation with adequate follow-up duration and histopathologic validation may be helpful in discriminating PsPD from true progression.

• The Korean Journal of Physiology and Pharmacology
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• 제18권6호
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• pp.447-456
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• 2014

Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) $A{\beta}_{1-42}$, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the clinical utility of CSF biomarkers and the integration of CSF biomarkers in current clinical trials.

• Biomolecules & Therapeutics
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• 제31권3호
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• pp.253-263
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• 2023

The biogenesis and biological roles of extracellular vesicles (EVs) in the progression of liver diseases have attracted considerable attention in recent years. EVs are membrane-bound nanosized vesicles found in different types of body fluids and contain various bioactive materials, including proteins, lipids, nucleic acids, and mitochondrial DNA. Based on their origin and biogenesis, EVs can be classified as apoptotic bodies, microvesicles, and exosomes. Among these, exosomes are the smallest EVs (30-150 nm in diameter), which play a significant role in cell-to-cell communication and epigenetic regulation. Moreover, exosomal content analysis can reveal the functional state of the parental cell. Therefore, exosomes can be applied to various purposes, including disease diagnosis and treatment, drug delivery, cell-free vaccines, and regenerative medicine. However, exosome-related research faces two major limitations: isolation of exosomes with high yield and purity and distinction of exosomes from other EVs (especially microvesicles). No standardized exosome isolation method has been established to date; however, various exosome isolation strategies have been proposed to investigate their biological roles. Exosome-mediated intercellular communications are known to be involved in alcoholic liver disease and nonalcoholic fatty liver disease development. Damaged hepatocytes or nonparenchymal cells release large numbers of exosomes that promote the progression of inflammation and fibrogenesis through interactions with neighboring cells. Exosomes are expected to provide insight on the progression of liver disease. Here, we review the biogenesis of exosomes, exosome isolation techniques, and biological roles of exosomes in alcoholic liver disease and nonalcoholic fatty liver disease.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6615-6619
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• 2015

Background: The expression of HER-2 in prostate cancer has been linked to disease progression. We analysed the presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its association with clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) during follow up, as well as links with biochemical failure and the effects of androgen blockade. Materials and Methods: Consecutive men undergoing radical prostatectomy for histologically confirmed prostate cancer were analyzed. HER-2 expression in the primary tumor was assessed using the HercepTest(R), CPCs were identified from blood samples using standard immunocytochemistry with anti-PSA and positive samples with the HercepTest(R) to determine HER-2 expression. The influence of HER-2 expression on the frequency of biochemical failure and effects of androgen blockade was determined. Results: 144 men with a mean age of $64.8{\pm}10.3$ years participated, with a median follow up of 8.2 years. HER-2 was expressed in 20.8% of primary tumors; it was associated with vascular infiltration and older age, but not with other clinical pathological findings. Some 40.3% of men had secondary CPCs detected, of which 38% expressed HER-2. Men CPC (+) had a higher frequency of biochemical failure, but there was no difference in HER-2 expression of CPCs with the frequency of biochemical failure. After androgen blockade, men with HER-2 (+) positive secondary CPCs had a higher frequency of disease progression to castrate resistant disease. Conclusions: HER-2 plays a dual role in the progression of prostate cancer; firstly it may increase the potential of tumor cells to disseminate from the primary tumor via the blood by increasing vascular infiltration. In the presence of androgens, there is no survival advantage of expressing HER-2, but once biochemical failure has occurred and androgen blockade started, HER-2 positive cells are resistant to treatment, survive and grow leading to castration resistant disease.