• Biomolecules & Therapeutics
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• v.28 no.3
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• pp.250-258
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• 2020

Emphysema, a major component of chronic obstructive pulmonary disease (COPD), is a leading cause of human death worldwide. The progressive deterioration of lung function that occurs in the disease is caused by chronic inflammation of the airway and destruction of the lung parenchyma. Despite the main impact of inflammation on the pathogenesis of emphysema, current therapeutic regimens mainly offer symptomatic relief and preservation of lung function with little therapeutic impact. In the present study, we aimed to discover novel therapeutics that suppress the pathogenesis of emphysema. Here, we show that LJ-2698, a novel and highly selective antagonist of the adenosine A₃ receptor, a G protein-coupled receptor involved in various inflammatory diseases, significantly reversed the elastase-induced destructive changes in murine lungs. We found that LJ-2698 significantly prevented elastase-induced airspace enlargement, resulting in restoration of pulmonary function without causing any obvious changes in body weight in mice. LJ-2698 was found to inhibit matrix metalloproteinase activity and pulmonary cell apoptosis in the murine lung. LJ-2698 treatment induced increases in anti-inflammatory cytokines in macrophages at doses that displayed no significant cytotoxicity in normal cell lines derived from various organs. Treatment with LJ-2698 significantly increased the number of anti-inflammatory M2 macrophages in the lungs. These results implicate the adenosine A₃ receptor in the pathogenesis of emphysema. Our findings also demonstrate the potential of LJ-2698 as a novel therapeutic/preventive agent in suppressing disease development with limited toxicity.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.335-343
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• 2017

Atopic dermatitis (AD) is an inflammatory skin condition accompanied by symptoms such as edema and hemorrhage. Kimchi is a traditional fermented Korean dish consisting of various probiotics. In this study, the therapeutic effect of Lactobacillus plantarum CJLP55 isolated from Kimchi was studied in AD-induced mice. Orally administered Lactobacillus strain, CJLP55, suppressed AD symptoms and high serum IgE levels. CJLP55 administration reduced the thickness of the epidermis, infiltration of mast cells and eosinophils into the skin lesion, enlargement of axillary lymph nodes, and increase in cell population in axillary lymph nodes. CJLP55 treatment decreased the production of type 2 cytokines, such as interleukin (IL)-4, IL-5, IL-10, IL-12, interferon (IFN)-${\gamma}$, and IL-6,which were stimulated by house dust mite extracts, in the axillary lymph node cells. Orally administered CJLP55 exhibited a therapeutic effect on house dust mite-induced AD in NC/Nga mice after onset of the disease by altering immune cell activation. The Lactobacillus strain, CJLP55, isolated from Kimchi, suppressed AD. Our results suggest its possible use as a potential candidate for management of AD.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.491-497
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• 2015

Traumatic brain injury (TBI) is a major cause of mortality and long-term disability, which can decrease quality of life. In spite of numerous studies suggesting that Epigallocatechin-3- gallate (EGCG) has been used as a therapeutic agent for a broad range of disorders, the effect of EGCG on TBI remains unknown. In this study, a weight drop model was established to evaluate the therapeutic potential of EGCG on TBI. Rats were administered with 100 mg/kg EGCG or PBS intraperitoneally. At different times following trauma, rats were sacrificed for analysis. It was found that EGCG (100 mg/kg, i.p.) treatment significantly reduced brain water content and vascular permeability at 12, 24, 48, 72 hour after TBI. Real-time PCR results revealed that EGCG inhibited TBI-induced IL-$1{\beta}$ and TNF-${\alpha}$ mRNA expression. Importantly, CD68 mRNA expression decreasing in the brain suggested that EGCG inhibited microglia activation. Western blotting and immunohistochemistry results showed that administering of EGCG significantly inhibited the levels of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression. TBI-induced oxidative stress was remarkably impaired by EGCG treatment, which elevated the activities of SOD and GSH-PX. Conversely, EGCG significantly reduced the contents of MDA after TBI. In addition, EGCG decreased TBI-induced NADPH oxidase activation through inhibition of $p47^{phox}$ translocation from cytoplasm to plasma membrane. These data demonstrate that EGCG treatment may be an effective therapeutic strategy for TBI and the underlying mechanism involves inhibition of oxidative stress.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9459-9465
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• 2014

Background: Structural maintenance of chromosomes 4 (SMC-4) is a chromosomal ATPase which plays an important role in regulate chromosome assembly and segregation. However, the role of SMC-4 in the incidence of malignancies, especially colorectal cancer is still poorly understood. Materials and Methods: We here used quantitative PCR and Western blot analysis to examine SMC-4 mRNA and protein levels in primary colorectal cancer and paired normal colonic mucosa. SMC-4 clinicopathological significance was assessed by immunohistochemical staining in a tissue microarray (TMA) in which 118 cases of primary colorectal cancer were paired with noncancerous tissue. The biological function of SMC-4 knockdown was measured by CCK8 and plate colony formation assays. Fluorescence detection has been used to detect cell cycling and apoptosis. Results: SMC-4 expression was significantly higher in colorectal cancer and associated with T stage, N stage, AJCC stage and differentiation. Knockdown of SMC-4 expression significantly suppressed the proliferation of cancer cells and degraded its malignant degree. Conclusions: Our clinical and experimental data suggest that SMC-4 may contribute to the progression of colorectal carcinogenesis. Our study provides a new therapeutic target for colorectal cancer treatment.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.6
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• pp.806-813
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• 2010

Animal bioreactors have been regarded as alternative tools for the production of limited human therapeutic proteins. The mammary glands of cattle are optimal tissues to produce therapeutic proteins that cannot be produced in large amounts in traditional systems based on microorganisms and eukaryotic cells. In this study, two knock-in vectors, pBCTPOKI-6 and pBCTPOKI-10, which target the hTPO gene on the bovine beta-casein locus, were designed to develop cloned transgenic cattle. The pBCTPOKI-6 and pBCTPOKI-10 vectors expressed hTPO protein in culture medium at a concentration of 774 pg/ml and 1,867 pg/ml, respectively. Successfully, two targeted cell clones were obtained from the bovine fibroblasts transfected with the pBCTPOKI-6 vector. Cloned embryos reconstructed with the targeted nuclei showed a lower in vitro developmental competence than those with the wild-type nuclei. After transfer of the cloned embryos into recipients, 7 pregnancies were detected at 40 to 60 days of gestation, but failed to develop to term. The results are the first trial for targeting of a human gene on the bovine milk protein gene locus, providing the potential for a large-scale production of therapeutic proteins in the animal bioreactor system.

• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.226-232
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• 2001

The pharmacotherapy of depression has reduced morbidity and improved outcome for many depressive patients. A wide range of classical and new antidepressants are available for their treatment. However, 30-40% of all patients do not respond sufficiently to the initial treatment and present adverse effects. Pharmacogenetics studies the genetic basis of an individual's ability to respond to pharmacotherapy. Recently, some reports on serotonin transporter gene polymorphisms and their influence on the response to antidepressive therapy provide an interesting diagnostic tool in assessing the chances of response to antidepressants. We also investigated the relationship between serotonin transprter polymorphisms(5-HTTLPR) and the long-term effect of the antidepressant treatment. 128 depressive patients were enrolled into 2nd year study. The therapeutic response of each subset was not different at 8th, 16th week, but the subset with homozygote(l/l) of long variant showed a better therapeutic response to antidepressant than the heterozygote(l/s) of long and short variant, which showed a better therapeutic response than the subset with homozygote (s/s) of short variant at 1st year and 2nd year after the antidepressant treatment. This result shows that the serotonin transporter polymorphisms may be related to the long-term effect of antidepressant treatment. The potential for pharmacogenomics, the use of genetic information to guide pharmacotherapy and improve outcome by providing individualized treatment decisions, has gained increasing attention. pharmacogenomics will contribute to individualize drug choice by using genotype to predict positive clinical outcomes, adverse reactions, and levels of drug metabolism. Personalized medicine, the use of marker-assisted diagnosis and targeted therapies derived from an individual molecular profile, will impact the antidepressant therapy and this approach will replace the traditional trial-and-error practice of medicine.

• Archives of Plastic Surgery
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• v.47 no.4
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• pp.305-309
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• 2020

Breast cancer treatment-related lymphedema (BCRL) is a common comorbidity in breast cancer survivors. Although magnetic resonance imaging (MRI) is widely used to evaluate therapeutic response of patients with various medical conditions, it is not routinely used to evaluate lymphedema patients. We conducted a systematic review of the literature to identify studies on the use of MRI to evaluate therapy for BCRL. We hypothesized that MRI could provide information otherwise not possible through other examinations. On October 21, 2019, we conducted a systematic review on the PubMed/MEDLINE and Scopus databases, without time frame or language limitations, to identify studies on the use of MRI to evaluate therapy for BCRL. We excluded studies that investigated other applications of MRI, such as lymphedema diagnosis and surgical planning. Of 63 potential articles identified with the search, three case series fulfilled the eligibility criteria. In total, 53 patients with BCRL were included and quantitatively evaluated with MRI before and after manual lymphatic drainage. Authors used MRI or MR lymphagiography to investigate factors such as lymphatic vessel cross-sectional area, tissue water relaxation time (T₂), and chemical exchange saturation transfer. The only study that compared MRI measurement with standard examinations reported that MRI added information to the therapy evaluation. MRI seems to be a promising tool for quantitative measurement of therapeutic response in patients with BCRL. However, the identified studies focused on only manual lymphatic drainage and were limited by the small numbers of patients. More studies are necessary to shed light on the topic.

• Korean Journal of Veterinary Research
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• v.56 no.2
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• pp.103-108
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• 2016

Salmonellosis is a major bacterial zoonosis that causes self-limited enteritis in animals and foodborne disease and typhoid fever in humans. Recently, multi-drug-resistant strains of Salmonella spp. have increased and caused more serious problems in public health. The present study investigated the antibacterial effects of egg-white lysozyme (EWL) against Salmonella (S.) Typhimurium and the therapeutic effects of EWL for murine salmonellosis. Evaluation of the antibacterial effects of EWL against S. Typhimurium revealed a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of EWL of 6.25 and $300{\mu}g/mL$, respectively. In the bacterial growth inhibition test, EWL at 300 (p < 0.05) and $600{\mu}g/mL$ (p < 0.01) significantly inhibited the growth of S. Typhimurium at 4 h post-incubation. EWL administration at MIC (LYS-1), MBC (LYS-2) and $2{\times}MBC$ (LYS-3) for 14 days resulted in mortality of mice infected with S. Typhimurium of 70, 40 and 10%, respectively, while that of control mice (CON) was 90%. Counts of S. Typhimurium in murine spleens were significantly lower in LYS-2 and LYS-3 than CON (p < 0.05). The results of this study indicate that EWL has the potential for treatment of ICR mice infected with S. Typhimurium.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.15 no.1
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• pp.127-139
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• 2002

This study was carried out to prove the therapeutic effects of BNJB on the catract. The objects of this study were CXSD mice that spontaneously eye rupture occurred from three weeks after birth and eventually generate cataract within 12 weeks. We applied eyewash made from BNJB to eyes of CXSD mice twice in a day till all the eyes of the negative control showed up the symptoms of a cataract and recorded the increasing patterns of cataractous eyes. To explained the therapeutic effects of the BNJB, We carried out the ex vivo experiment which cultivating eyeballs were offered oxidative stress condition by $0.03{\%}$ $H_2O_2$ during three days. Total co-enzyme was extracted from the cultured eyeballs and used to measure activities of catalase, superoxide dismutase, glutathion S-transferase and content of GSH. The results were obtained as follows: 1. When we treated the catalin to CXSD mouse as a positive control, it represented the delaying effect for cataract generation for 2-3 days compare with negative control. But it seems that it doesn't appropriate as a therapeutic, or delaying agent. 2. In the experimental BNJB group, Cataract formation rate was dramatically reduced by BNJB. This rate was much lower than positive group and means our new formulation for the therapy of cataract has a good potential. 3. In the analysis of individual medicines of BNJB, Mok-Jeok-Cho, Hwang-Lyun and Ha-Go-Cho didn't have a major effect of BNJB. 4. The cataract formation rate was repressed by Bing-Pyun and Jin- Joo-Boon about $40{\%}$ and $50{\%}$, respectively. We can presume that the anti-cataract effect of BNJB was caused by these two medicines. 5. When we surveyed the anti-oxidant activities of BNJB, enzyme activities of GSH, SOD, and Catalase increased about $10{\%},\30{\%}$, and 2.5 folds, respectively.

• Journal of Ginseng Research
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• v.42 no.3
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• pp.379-388
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• 2018

Background: Ginsenosides are the main ingredients of Korean Red Ginseng. They have extensively been studied for their beneficial value in neurodegenerative diseases such as Parkinson's disease (PD). However, the multitarget effects of Korean Red Ginseng extract (KRGE) with various components are unclear. Methods: We investigated the multitarget activities of KRGE on neurological dysfunction and neurotoxicity in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. KRGE (37.5 mg/ kg/day, 75 mg/kg/day, or 150 mg/kg/day, per os (p.o.)) was given daily before or after MPTP intoxication. Results: Pretreatment with 150 mg/kg/day KRGE produced the greatest positive effect on motor dysfunction as assessed using rotarod, pole, and nesting tests, and on the survival rate. KRGE displayed a wide therapeutic time window. These effects were related to reductions in the loss of tyrosine hydroxylase-immunoreactive dopaminergic neurons, apoptosis, microglial activation, and activation of inflammatory factors in the substantia nigra pars compacta and/or striatum after MPTP intoxication. In addition, pretreatment with KRGE activated the nuclear factor erythroid 2-related factor 2 pathways and inhibited phosphorylation of the mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways, as well as blocked the alteration of blood-brain barrier integrity. Conclusion: These results suggest that KRGE may effectively reduce MPTP-induced neurotoxicity with a wide therapeutic time window through multitarget effects including antiapoptosis, antiinflammation, antioxidant, and maintenance of blood-brain barrier integrity. KRGE has potential as a multitarget drug or functional food for safe preventive and therapeutic strategies for PD.