Chlorin e6 Prevents ADP-Induced Platelet Aggregation by Decreasing PI3K-Akt Phosphorylation and Promoting cAMP Production

Park, Ji Young,Ji, Hyun Dong,Jeon, Bo Ra,Im, Eun Ju,Son, Young Min,Lee, Joo Young,Lee, Dong-Ha,Lee, Young-Chul,Hyun, Eujin,Jia, Qi,Hong, Mei,Park, Hwa-Jin,Rhee, Man Hee Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

<P>A number of reagents that prevent thrombosis have been developed but were found to have serious side effects. Therefore, we sought to identify complementary and alternative medicinal materials that are safe and have long-term efficacy. In the present studies, we have assessed the ability of chlorine e6 (CE6) to inhibit ADP-induced aggregation of rat platelets and elucidated the underlying mechanism. CE6 inhibited platelet aggregation induced by 10 <I>µ</I>M ADP in a concentration-dependent manner and decreased intracellular calcium mobilization and granule secretion (i.e., ATP and serotonin release). Western blotting revealed that CE6 strongly inhibited the phosphorylations of PI3K, Akt, c-Jun N-terminal kinase (JNK), and different mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2) as well as p38-MAPK. Our study also demonstrated that CE6 significantly elevated intracellular cAMP levels and decreased thromboxane A<SUB>2</SUB> formation in a concentration-dependent manner. Furthermore, we determined that CE6 initiated the activation of PKA, an effector of cAMP. Taken together, our findings indicate that CE6 may inhibit ADP-induced platelet activation by elevating cAMP levels and suppressing PI3K/Akt activity. Finally, these results suggest that CE6 could be developed as therapeutic agent that helps prevent thrombosis and ischemia.</P>

Identification of indirect effects in the two-condition within-subject mediation model and its implementation using SEM

Park Eujin,Park Changsoon 한국통계학회 2023 Communications for statistical applications and me Vol.30 No.6

In the two-condition within-subject mediation design, pairs of variables such as mediator and outcome are observed under two treatment conditions. The main objective of the design is to investigate the indirect effects of the condition difference (sum) on the outcome difference (sum) through the mediator difference (sum) for comparison of two treatment conditions. The natural condition variables mean the original variables, while the rotated condition variables mean the difference and the sum of two natural variables. The outcome difference (sum) is expressed as a linear model regressed on two natural (rotated) mediators as a parallel two-mediator design in two condition approaches: the natural condition approach uses regressors as the natural condition variables, while the rotated condition approach uses regressors as the rotated condition variables. In each condition approach, the total indirect effect on the outcome difference (sum) can be expressed as the sum of two individual indirect effects: within- and cross-condition indirect effects. The total indirect effects on the outcome difference (sum) for both condition approaches are the same. The invariance of the total indirect effect makes it possible to analyze the nature of two pairs of individual indirect effects induced from the natural conditions and the rotated conditions. The two-condition within-subject design is extended to the addition of a between-subject moderator. Probing of the conditional indirect effects given the moderator values is implemented by plotting the bootstrap confidence intervals of indirect effects against the moderator values. The expected indirect effect with respect to the moderator is derived to provide the overall effect of moderator on the indirect effect. The model coefficients are estimated by the structural equation modeling approach and their statistical significance is tested using the bias-corrected bootstrap confidence intervals. All procedures are evaluated using function lavaan() of package \{lavaan\} in R.

X-linked hypophosphatemic rickets: from diagnosis to management

Eujin Park,Hee Gyung Kang 대한소아청소년과학회 2024 Clinical and Experimental Pediatrics (CEP) Vol.67 No.1

X-linked hypophosphatemia (XLH), the most common cause of hypophosphatemic rickets, affects one in every 20,000 people. Although conventional therapy for XLH was introduced approximately 4 decades ago, the temporary replacement of oral phosphate salts and activated vitamin D cannot completely control chronic hypophosphatemia, leaving patients with incomplete healing and residual skeletal deformity as well as at risk of endocrine abnormalities and adverse drug reactions. However, understanding the pathophysiology has led to the development of a targeted therapy, burosumab, a fibroblast growth factor-23 inhibitor that was recently approved in Korea for the treatment of XLH. This review provides insight into the diagnosis, evaluation, treatment, and recommendedfollow-up for a typical case of XLH and reviews its pathophysiology.

Genetic Basis of Steroid Resistant Nephrotic Syndrome

Park, Eujin Korean Society of Pediatric Nephrology 2019 Childhood kidney diseases Vol.23 No.2

Steroid-resistant nephrotic syndrome (SRNS) has long been a challenge for clinicians due to its poor responsiveness to immunosuppressants, and rapid progression to end-stage renal disease. Identifying a monogenic cause for SRNS may lead to a better understanding of podocyte structure and function in the glomerular filtration barrier. This review focuses on genes associated with slit diaphragm, actin cytoskeleton, transcription factors, nucleus, glomerular basement membrane, mitochondria, and other proteins that affect podocyte biology.

Disseminated adenovirus infection in a 10-year-old renal allograft recipient

( Eujin Park ),( Hee Gyung Kang ),( Hae Il Cheong ),( Il Soo Ha ),( Bora Lee ),( Jongwon Ha ) 대한신장학회 2018 Kidney Research and Clinical Practice Vol.37 No.4

Primary Autosomal Recessive Distal Renal Tubular Acidosis Caused by a Common Homozygous <i>SLC4A1</i> Mutation in Two Lao Families

Park, Eujin,Phaymany, Vilaphone,Yi, Eun Sang,Phangmanixay, Sommanikhone,Cheong, Hae Il,Choi, Yong KOREAN ACADEMY OF MEDICAL SCIENCE 2018 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.33 No.13

<P>Primary distal renal tubular acidosis (dRTA) caused by mutations of the <I>SLC4A1</I> gene, which encodes for erythroid and kidney isoforms of anion exchanger, shows marked difference in inheritance patterns and clinical features in different parts of the world. While the disease shows autosomal dominant inheritance without any red cell morphological abnormalities in the temperate countries, it is almost invariably recessive, and often accompanies red cell morphological abnormalities or hemolytic anemia in the tropics, especially in Southeast Asia. Here, we report three patients with autosomal recessive (AR) dRTA, presenting with typical findings of failure to thrive and rickets, from two unrelated Lao families. The mutational analyses revealed that all three patients harbored the same homozygous <I>SLC4A1</I> mutation, p.Gly701Asp. Adequate supplementation of alkali and potassium resulted in remarkable improvement of growth retardation and skeletal deformities of the patients. This is the first case report of Lao patients with AR dRTA caused by <I>SLC4A1</I> mutations.</P>

Genotype–Phenotype Analysis in Pediatric Patients with Distal Renal Tubular Acidosis

Park, Eujin,Cho, Myung Hyun,Hyun, Hye Sun,Shin, Jae Il,Lee, Joo Hoon,Park, Young Seo,Choi, Hyun Jin,Kang, Hee Gyung,Cheong, Hae Il Karger Medical and Scientific Publishers 2018 Kidney & blood pressure research Vol. No.

<P>Background/Aims: Primary distal renal tubular acidosis (dRTA) in children is a rare genetic disorder, and three causative mutated genes have been identified: SLC4A1, ATP6V1B1, and ATP6V0A4. We analyzed the prevalence and phenotypic differences of genetic mutations in children with dRTA. Methods: A total of 17 children with dRTA were enrolled in the study. All patients underwent genetic testing for all three candidate genes. Results: Pathogenic mutations, including six novel mutations, were detected in 15 (88.2%) patients: dominant SLC4A1 mutations in ten (58.8%) patients, recessive ATP6V0A4 mutations in three (17.6%) patients, and recessive ATP6V1B1 mutations in two (11.8%) patients. Compared to other patients, patients with SLC4A1 mutations showed an older age of onset (3.7 +/- 2.6 years) and less severe metabolic acidosis at initial presentation. All patients developed nephrocalcinosis, and sensorineural hearing loss was observed in two patients with ATP6V1B1 mutations. Three (17.6%) patients had decreased renal function (chronic kidney disease stage 2), and five (29.4%) patients had persistent growth retardation at the last follow-up. Long-term prognosis showed no genotype-phenotype correlation. Conclusions: SLC4A1 is the most common defective gene in Korean children with dRTA. Patients with SLC4A1 mutations show later onset and milder disease severity. Long-term follow-up of hearing ability, renal function, and growth is necessary for patients with (C) 2018 The Author(s) Published by S. Karger AG, Basel.</P>

Genetic Basis of Steroid Resistant Nephrotic Syndrome

Eujin Park 대한소아신장학회 2019 Childhood kidney diseases Vol.23 No.2

Steroid-resistant nephrotic syndrome (SRNS) has long been a challenge for clinicians due to its poor responsiveness to immunosuppressants, and rapid progression to end-stage renal disease. Identifying a monogenic cause for SRNS may lead to a better understanding of podocyte structure and function in the glomerular filtration barrier. This review focuses on genes associated with slit diaphragm, actin cytoskeleton, transcription factors, nucleus, glomerular basement membrane, mitochondria, and other proteins that affect podocyte biology.

Inhibition of the renin-angiotensin system during fetal kidney development

Park, Eujin The Korean Pediatric Society 2021 Clinical and Experimental Pediatrics (CEP) Vol.64 No.3

Anti-inflammatory Effects of KOTMIN13: A Mixed Herbal Medicine in LPS-stimulated RAW 264.7 Cells and Mouse Edema Models

Lee, Eujin,Kim, Sun-Gun,Park, Na-Young,Park, Hyo-Hyun,Jeong, Kyu-Tae,Choi, Jongkeun,Lee, In-Hae,Lee, Hwadong,Lee, Eunkyung Medknow PublicationsMedia Pvt Ltd 2017 Pharmacognosy magazine Vol.13 No.50

<P><B>Background:</B></P><P>A Korean herbal medicine, KOTMIN13, composed of <I>Inula japonica</I> Thunberg, <I>Trichosanthes kirilowii Maximowicz</I> var. <I>japonica kitamura</I>, <I>Peucedanum praeruptorum</I> Dunn, and <I>Allium macrostemon</I> Bge, has been used for anti-allergic and anti-asthmatic treatment in oriental clinics, but its activity has not been investigated.</P><P><B>Materials and Methods:</B></P><P>To evaluate the anti-inflammatory activity of KOTMIN13 for <I>in vitro</I> study, LPS-stimulated RAW 264.7 cells were used to induce the production and expression of inflammatory mediators and its mechanisms. 12-<I>O</I>-Tetradecanoylphorobol-13 aceate (TPA)-induced ear edema and carrageenan-induced paw edema models were also used to evaluate the effect of KOTMIN13 on acute inflammation <I>in vivo</I>.</P><P><B>Results:</B></P><P>KOTMIN13 reduced the release of inflammatory mediators [nitric oxide, prostaglandin E2, interleukin (IL)-1β, and IL-6] and the protein expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells. Mechanism studies showed the attenuation of LPS-induced NF-κB activation by KOTMIN13 via IκBα degradation abrogation and a subsequent decrease in nuclear p65 levels. Activation of mitogen-activated protein kinases (ERK, JNK, and p38) was also suppressed. Furthermore, KOTMIN13 ameliorated the development of TPA-induced ear edema and carrageenan-induced paw edema in acute inflammatory edema mouse models.</P><P><B>Conclusion:</B></P><P>Our study demonstrates that KOTMIN13 inhibits inflammatory mediators through the inhibitions of NF-κB and MAPK activities in LPS-induced RAW 264.7 cells, as well as acute inflammation in edema models, indicating that KOTMIN13 is an effective suppressor for anti-inflammatory activities.</P><P><B>SUMMARY</B></P><P><P>KOTMIN13 decrease the production of No, PGE<SUB>2</SUB>, and proinflammatory cytokine (TNF-∝, IL-1β,IL-6).</P><P>KOTMIN13 Suppressed the degradation of NF-kβ and IKβα and the phosorylation of MAP Kinases.</P><P>Topical application of KOTMIN13 reduced mouse ear edema.</P><P>Oral administration of KOTMIN13 decreased carrageenan-induced paw edema.</P></P> >[FIG OMISSION]</BR><P><B>Abbreviations used:</B> NO: nitric oxide; PGE2: prostaglandin E2; iNOS: inducible NO synthase; COX-2: cyclooxygenase-2; TNF-α: tumor necrosis factor-α; IL: interleukin; NF-κB: nuclear factor kappaB; MAPK: mitogen-activated protein kinases; ERK: extracellular signal regulated kinase; JNK: c-jun N terminal kinase; TPA: 12-O-tetradecanoylphorbol-13-acetate</P>