• BMB Reports
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• v.38 no.1
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• pp.9-16
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• 2005

Transforming Growth Factor (TGF)-$\beta$ family, including TGF-$\beta$, bone morphorgenic protein (BMP), and activn, plays an important role in essential cellular functions such as proliferation, differentiation, apoptosis, tissue remodeling, angiognesis, immune responses, and cell adhesions. TGF-$\beta$ predominantly transmits the signals through serine/threonine receptor kinases and cytoplasmic proteins called Smads. Since the discovery of TGF-$\beta$ in the early 1980s, the dysregulation of TGF-$\beta$/Smad signaling has been implicated in the pathogenesis of human diseases. Among signal transducers in TGF-$\beta$/Smad signaling, inhibitory Smads (I-Smads), Smad6 and Smad7, act as major negative regulators forming autoinhibitory feedback loops and mediate the cross-talking with other signaling pathways. Expressions of I-Smads are mainly regulated on the transcriptional levels and post-translational protein degradations and their intracellular levels are tightly controlled to maintain the homeostatic balances. However, abnormal levels of I-Smads in the pathological conditions elicit the altered TGF-$\beta$ signaling in cells, eventually causing TGF-$\beta$-related human diseases. Thus, exploring the molecular mechanisms about the regulations of I-Smads may provide the therapeutic clues for human diseases induced by the abnormal TGF-$\beta$ signaling.

• Molecules and Cells
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• v.41 no.1
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• pp.55-64
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• 2018

Autophagy is an intracellular degradation pathway for large protein aggregates and damaged organelles. Recent studies have indicated that autophagy targets cargoes through a selective degradation pathway called selective autophagy. Peroxisomes are dynamic organelles that are crucial for health and development. Pexophagy is selective autophagy that targets peroxisomes and is essential for the maintenance of homeostasis of peroxisomes, which is necessary in the prevention of various peroxisome-related disorders. However, the mechanisms by which pexophagy is regulated and the key players that induce and modulate pexophagy are largely unknown. In this review, we focus on our current understanding of how pexophagy is induced and regulated, and the selective adaptors involved in mediating pexophagy. Furthermore, we discuss current findings on the roles of pexophagy in physiological and pathological responses, which provide insight into the clinical relevance of pexophagy regulation. Understanding how pexophagy interacts with various biological functions will provide fundamental insights into the function of pexophagy and facilitate the development of novel therapeutics against peroxisomal dysfunction-related diseases.

• Journal of Chest Surgery
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• v.23 no.4
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• pp.676-682
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• 1990

From August, 1978, to August, 1989, 22 patients underwent pericardiectomy for chronic constrictive pericarditis on the Department of Thoracic and Cardiovascular Surgery, School of Medicine, Keimyung University. There were 14 male and 6 female patients ranging from 11 years to 70 years old[mean age, 44. 1 years]. All patients underwent radical pericardiectomy through a median sternotomy. There was 1 postoperative death[4.s%]. This patient died of low cardiac output 7 days after pericardiectomy. Postoperative complications were hemothorax[2 patients], low cardiac output[2 patients], generalized seizure[1 patient], wound infection[1 patient] and pneumonia[1 patient]. Clinical and pathological findings showed tuberculous origin in 12 patients[54.6%], unknown etiology in 8 patients[36.4%] pyogenic pericarditis in 2 patients[9.1%]. Three hemodynamic responses to pericardiectomy were observed: [1] rapid response, where central venous pressure[CUP] fell below 10 cmH2O by 24 hours in 6 patients; [2] delayed response. Where CVP fell below 10 cmH2O by 48 hours in 12 patients; and [3] no response of CVP in 4 patients. Follow-up ranged from 6 to 62 months with an average of 35.3 months. Postoperative Functional Class was obtained for 21 surviving patients and showed 18 patients[81.8%] to be New York Heart Association functional class I or II.

• Toxicological Research
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• v.13 no.4
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• pp.353-357
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• 1997

The possibility of the allergic encephalomyelitis caused by the combined vaccine (KGCC95VI) for the prophylaxis against Japanese encephalitis and Hantaan virus infection, recently developed by Korea Green Cross Corporation, was investigated in the Hartley guinea pigs. The KGCC-95VI was administered to the guinea pigs subcutaneously to sensitize the animals three times at one month intervals. There were no clinical signs or gross pathological findings. There were no abnormal histopathological findings at cerebrums, cerebellums, brain stems and the spinal cords. The concentration of myelin basic protein was 1.10 ng/dose quantified by ELISA, which met the guide4ine of below 2 ng/ml/dose recommended by American Society of Health -System Pharmacists(AHPS) Drug Information. Accordingly, the KGCC-95VI is considered not to induce any allergic immune responses which may lead to the experimental allergic encephalomyelitis.

• CELLMED
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• v.4 no.4
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• pp.26.1-26.9
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• 2014

Reactive oxygen species are known to mediate various pathological conditions associated with malaria. In this study, the antioxidant potential of Clerodendrum violaceum leaf extracts, an indigenous antimalarial remedy, was evaluated. Total phenol, flavonoid, selenium, vitamins C and E contents of Clerodendrum violaceum leaf extracts were determined. The free radical scavenging activities of the extracts against DPPH, superoxide anion and hydrogen peroxide coupled with their reducing power were also evaluated in vitro. Moreover, responses of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in a rodent malaria model to a 4-day administration of Clerodendrum violaceum leaf extracts were also evaluated. The methanolic extract was found to contain the highest amounts of antioxidant compounds/element and also demonstrated the highest free radical scavenging activity in vitro. The results showed a significant decrease (p < 0.05) in SOD and CAT activities with a concurrent significant (p < 0.05) increase in GPx and GR activities in both erythrocytes and liver of untreated Plasmodium berghei NK65-infected animals compared to the uninfected animals. The extracts were able to significantly increase (p < 0.05) SOD and CAT activities and significantly reduce (p < 0.05) GPx and GR activities in both the liver and erythrocytes compared to those observed in the untreated infected animals. The results suggest the augmentation of the antioxidant system as one of the possible mechanisms by which Clerodendrum violaceum extract ameliorates secondary effects of malaria infection, alongside its antiplasmodial effect in subjects.

• Molecules and Cells
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• v.25 no.3
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• pp.347-351
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• 2008

Several lines of evidence indicate that the oxidative modification of protein and the subsequent accumulation of the modified proteins have been found in cells during aging, oxidative stress, and in various pathological states including premature diseases, muscular dystrophy, rheumatoid arthritis, and atherosclerosis. The important agents that give rise to the modification of a protein may be represented by reactive aldehydic intermediates, such as ketoaldehydes, 2-alkenals and 4-hydroxy-2-alkenals. These reactive aldehydes are considered important mediators of cell damage due to their ability to covalently modify biomolecules, which can disrupt important cellular functions and can cause mutations. Furthermore, the adduction of aldehydes to apolipoprotein B in low-density lipoproteins (LDL) has been strongly implicated in the mechanism by which LDL is converted to an atherogenic form that is taken up by macrophages, leading to the formation of foam cells. During the search for an endogenous inducer of cyclooxygenase-2 (COX-2), an inducible isoform responsible for high levels of prostaglandin production during inflammation and immune responses, 4-hydroxy-2-noennal (HNE), one of the most representative lipid peroxidation product, has been identified as the potential inducer of COX-2. In addition, the following study on the molecular mechanism of the COX-2 induction by HNE has unequivocally established that a serum component, which is eventually identified to be denatured LDL, is essential for COX-2 induction. Here I review current understanding of the mechanisms by which HNE in cooperation with the serum component activates gene expression of COX-2.

• International Journal of Concrete Structures and Materials
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• v.11 no.2
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• pp.403-413
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• 2017

Residual axial capacity from numerical analysis was widely used as a critical indicator for damage assessment of reinforced concrete (RC) columns subjected to blast loads. However, the convergence of the numerical result was generally based on the displacement response, which might not necessarily generate the correct post-blast results in case that the strain softening behavior of concrete was considered. In this paper, two widely used concrete models are adopted for post-blast analysis of a RC column under blast loading, while the calculated results show a pathological mesh size dependence even though the displacement response is converged. As a consequence, a nonlocal integral formulation is implemented in a concrete damage model to ensure mesh size independent objectivity of the local and global responses. Two numerical examples, one to a RC column with strain softening response and the other one to a RC column with post-blast response, are conducted by the nonlocal damage model, and the results indicate that both the two cases obtain objective response in the post-peak stage.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.309-323
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• 2011

MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs of about 22 nucleotides that have recently emerged as important regulators of gene expression at the posttranscriptional level. Recent studies provided clear evidence that microRNAs are abundant in the lung, liver and kidney and modulate a diverse spectrum of their functions. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as infectious diseases, sickle cell disease and endometrium diseases as well as lung, liver and kidney diseases. As a consequence of extensive participation of miRNAs in normal functions, alteration and/or abnormalities in miRNAs should have importance in human diseases. Beside their important roles in patterning and development, miRNAs also orchestrated responses to pathogen infections. Particularly, emerging evidence indicates that viruses use their own miRNAs to manipulate both cellular and viral gene expression. Furthermore, viral infection can exert a profound impact on the host cellular miRNA expression profile, and several RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Here I briefly summarize the newly discovered roles of miRNAs in various human diseases including infectious diseases, sickle cell disease and enodmetrium diseases as well as lung, liver and kidney diseases.

• BMB Reports
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• v.55 no.2
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• pp.65-71
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• 2022

Regenerative medicine is a research field that develops methods to restore damaged cell or tissue function by regeneration, repair or replacement. Stem cells are the raw material of the body that is ultimately used from the point of view of regenerative medicine, and stem cell therapy uses cells themselves or their derivatives to promote responses to diseases and dysfunctions, the ultimate goal of regenerative medicine. Stem cell-derived extracellular vesicles (EVs) are recognized as an attractive source because they can enrich exogenous microRNAs (miRNAs) by targeting pathological recipient cells for disease therapy and can overcome the obstacles faced by current cell therapy agents. However, there are some limitations that need to be addressed before using miRNA-enriched EVs derived from stem cells for multiplexed therapeutic targeting in many diseases. Here, we review various roles on miRNA-based stem cell EVs that can induce effective and stable functional improvement of stem cell-derived EVs. In addition, we introduce and review the implications of several miRNA-enriched EV therapies improved by multiplexed targeting in diseases involving the circulatory system and nervous system. This systemic review may offer potential roles for stem cell-derived therapeutics with multiplexed targeting.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.12.1-12.17
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• 2024

Exosomes are double phospholipid membrane vesicles that are synthesized and secreted by a variety of cells, including T cells, B cells, dendritic cells, immune cells, are extracellular vesicles. Recent studies have revealed that exosomes can play a significant role in under both physiological and pathological conditions. They have been implicated in regulation of inflammatory responses, immune response, angiogenesis, tissue repair, and antioxidant activities, particularly in modulating immunity in autoimmune diseases (AIDs). Moreover, variations in the expression of exosome-related substances, such as miRNA and proteins, may not only offer valuable perspectives for the early warning, and prognostic assessment of various AIDs, but may also serve as novel markers for disease diagnosis. This article examines the impact of exosomes on the development of AIDs and explores their potential for therapeutic application.