• Journal of Ginseng Research
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• v.44 no.3
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• pp.386-398
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• 2020

Tissue fibrosis is an eventual pathologic change of numerous chronic illnesses, which is characterized by resident fibroblasts differentiation into myofibroblasts during inflammation, coupled with excessive extracellular matrix deposition in tissues, ultimately leading to failure of normal organ function. Now, there are many mechanistic insights into the pathogenesis of tissue fibrosis, which facilitate the discovery of effective antifibrotic drugs. Moreover, many chronic diseases remain a significant clinical unmet need. For the past five years, many research works have undoubtedly addressed the functional dependency of ginsenosides in different types of fibrosis and the successful remission in various animal models treated with ginsenosides. Caveolin-1, interleukin, thrombospondin-1 (TSP-1), liver X receptors (LXRs), Nrf2, microRNA-27b, PPARδ-STAT3, liver kinase B1 (LKB1)-AMPK, and TGF-β1/Smads are potential therapy targeting using ginsenosides. Ginsenosides can play a targeting role and suppress chronic inflammatory response, collagen deposition, and epitheliale-mesenchymal transition (EMT), as well as myofibroblast activation to attenuate fibrosis. In this report, our aim was to focus on the therapeutic prospects of ginsenosides in fibrosis-related human diseases making use of results acquired from various animal models. These findings should provide important therapeutic clues and strategies for the exploration of new drugs for fibrosis treatment.

• BMB Reports
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• v.50 no.2
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• pp.58-59
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• 2017

The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the $TGF{\beta}$/Smad-signaling. Antagonizing the milk fat globule-EGF factor 8 (MFGE8) activity blocked the anti-fibrotic effects of the MSC secretome in vitro and in vivo. Moreover, MFGE8 was secreted by MSCs from the umbilical cord as well as other tissues, including teeth and bone marrow. Administration of recombinant MFGE8 protein alone had a significant anti-fibrotic effect in two different models of liver fibrosis. Additionally, MFGE8 downregulated $TGF{\beta}$ type I receptor expression by binding to ${\alpha}v{\beta}3$ integrin on HSCs. These findings revealed the potential role of MFGE8 in modulating $TGF{\beta}$-signaling. Thus, MFGE8 could serve as a novel therapeutic agent for liver fibrosis.

• BMB Reports
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• v.52 no.7
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• pp.451-456
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• 2019

NDRG1 has been reported to exert pivotal roles in tumor progression and metastasis via Wnt/${\beta}$-catenin signaling pathway. However, little is known about the role of NDRG3 in hepatocarcinogenesis despite its classification in the same subfamily of NDRG1. The present study was aimed to characterize the expression pattern and understand the biological roles of NDRG3 in hepatocarcinogenesis, as a means to exploit its therapeutic potential. It was observed that NDRG3 was up-regulated in HCC tissues and higher NDRG3 expression was associated with significantly shorter overall survival. Furthermore, a lower level of NDRG3 exhibited marked positive correlation with metastasis-free survival. In vitro and in vivo experiments revealed that knock-down of NDRG3 inhibits HCC metastasis and angiogenesis. We further demonstrated that activation of WNT/${\beta}$-catenin signaling and enhanced CSC-like properties were responsible for NDRG3-mediated promoting effect on HCC. In conclusion, the principal findings demonstrated that high NDRG3 expression facilitates HCC metastasis via regulating the turnover of ${\beta}$-catenin, as well as provides a potential therapeutic target for future therapeutic interventions.

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.55-63
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• 2022

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to exert protective effects against several neurological diseases through its anti-oxidative and anti-inflammatory activities. The goal of the present study was to evaluate the therapeutic potential of OA against acute and chronic brain injuries after ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO, MCAO/reperfusion). OA administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, functional neurological deficits, and neuronal apoptosis. Moreover, delayed administration of OA (at 3 h after reperfusion) attenuated brain infarction and improved functional neurological deficits during the acute phase. Such neuroprotective effects were associated with attenuation of microglial activation and lipid peroxidation in the injured brain after the tMCAO challenge. OA also attenuated NLRP3 inflammasome activation in activated microglia during the acute phase. In addition, daily administration of OA for 7 days starting from either immediately after reperfusion or 1 day after reperfusion significantly improved functional neurological deficits and attenuated brain tissue loss up to 21 days after the tMCAO challenge; these findings supported therapeutic effects of OA against ischemic stroke-induced chronic brain injury. Together, these findings showed that OA exerted neuroprotective effects against both acute and chronic brain injuries after tMCAO challenge, suggesting that OA is a potential therapeutic agent to treat ischemic stroke.

• YAKHAK HOEJI
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• v.56 no.2
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• pp.126-135
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• 2012

Purpose: To develop therapeutic duplication criteria for the drugs used for respiratory diseases. Method: Therapeutic duplication was defined as "more than 2 drug ingredient-usage in which each has the same therapeutic effect and combination therapy does not confer additional therapeutic benefit". Respiratory system drugs approved in Korea were examined for the study. The WHO's Anatomical Therapeutic Chemical Classification System was used for grouping of the corresponding drug ingredients. The principles and recommendations on combination usage or multiple drug regimens were reviewed by using the clinical practice guidelines, textbooks, product labelings, and clinical articles. Clinical expert group consultation was performed and expert opinions were incorporated into the final criteria. Results: Nine hundred sixty two drug products with Korean Food and Drug Administration classification codes of 141, 149, 222, and 229 were evaluated, of which 87 active ingredients were composed. The drug ingredients were classified into 12 groups (antihistamines, oral nasal decongestants, leukotriene receptor antagonists, inhaled anticholinergics, inhaled corticosteroids, oral ${\beta}2$-agonists, long-acting ${\beta}2$-agonists, short-acting ${\beta}2$-agonists, xanthines, antiallergics, mucolytics and cough suppressants). The use of more than 2 drug ingredients including the same group was therapeutic duplication, and thus combination should be recommended not to be used. Conclusion: Twelve drug groups were identified as therapeutic duplication criteria. Combination therapy within each group should not be used otherwise therapeutic benefits outweigh potential risks.

• CELLMED
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• v.2 no.3
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• pp.24.1-24.5
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• 2012

Obesity is psychological and socioeconomic problems as well as health problems related to physical disease and disorder. The obesity epidemic, including a marked increase in the prevalence of obesity among pregnant women, represents a critical public health problem throughout the world. Gung-Gui-Tang (GGT), a prescription of traditional Korean medicine, has been used to treat dizziness due to loss of blood as well as static blood after childbirth. However, the therapeutic potential of GGT on postpartum obesity has not been fully elucidated in an experimental model. In our research, GGT inhibited the increases of body weight and adipose tissues in postpartum mice fed a high-fat diet. GGT also inhibited the elevations of plasma lipid profiles such as triglyceride, low-density lipoprotein cholesterol, total cholesterol, and glutamate pyruvate transaminase. Overall, these results provide evidence that GGT can help to inhibit postpartum obesity and open new perspective to recover the shape of mother into the moment of conception.

• BMB Reports
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• v.48 no.4
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• pp.193-199
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• 2015

Degenerative retinal diseases affect millions of people worldwide, which can lead to the loss of vision. However, therapeutic approaches that can reverse this process are limited. Recent efforts have allowed the possibility of the stem cell-based regeneration of retinal cells and repair of injured retinal tissues. Although the direct differentiation of pluripotent stem cells into terminally differentiated photoreceptor cells comprises one approach, a series of studies revealed the intrinsic regenerative potential of the retina using endogenous retinal stem cells. Muller glial cells, ciliary pigment epithelial cells, and retinal pigment epithelial cells are candidates for such retinal stem cells that can differentiate into multiple types of retinal cells and be integrated into injured or developing retina. In this review, we explore our current understanding of the cellular identity of these candidate retinal stem cells and their therapeutic potential for cell therapy against degenerative retinal diseases. [BMB Reports 2015; 48(4): 193-199]

• Journal of Animal Reproduction and Biotechnology
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• v.34 no.2
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• pp.70-74
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• 2019

The kidney is a highly complex organ, and acute or chronic renal diseases can occur with various complications such as diabetes and hypertension. So far, no target specific treatment is available in acute or chronic renal failure, necessitating the development of alternative therapeutic strategy. Recent experimental findings suggest that the renal function and structure can be restored after being treated with various sources of stem/progenitor cells. In this review, we discuss up-to-date findings of the potential of renal progenitor/stem cells in alleviating renal injuries with a focus on preclinical studies. We also review cellular mechanisms underlying the therapeutic function of these cells.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.155-173
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• 2011

Humans have and hold 100 trillion intestinal bacteria that are essential for health. For millions of years human-microorganisms interaction has co-evolved, and maintained close symbiotic relationship. Gut bacteria contributes to human health and metabolism, and humans provides the optimum nutrition-rich environment for bacteria. What is the mechanism of the host distinguishing the intestinal bacteria as its cohabiting partner and what kind of benefits does the gut microbiota provide the human are the fundamental questions to be asked and solved in order to make human life a higher quality. This review explains the physiological relationship and mutualism between the host and gut microorganism, and highlights the potential therapeutic approach for treating diseases, maintaining and improving health based on these correlations.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4873-4878
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• 2012

Apoptosis is programmed cell death which is essential for development and survival of living organisms. It is a sequentially regulated suicidal programme where cells activate certain enzymes which dissolute their own nuclear component and various protein component of nucleus and cytoplasm. Disturbance of this regulatory pathway may lead to various diseases like autoimmune diseases, neurodegenerative diseases and cancers. The potential mechanisms of apoptosis and its role in cancer are discussed. The ability of apoptosis to modulate the life or death of a cell is also recognized for its immense therapeutic potential. Understanding the mechanisms from this review will give us better insight to the pathogenesis of various diseases including cancer and will open new horizons to therapeutic approaches.