Publications by authors named "Jin Hee Park"

212 Publications

The association of plasma osteoprotegerin levels and functional outcomes post endovascular thrombectomy in acute ischemic stroke patients: a retrospective observational study.

PeerJ 2022 3;10:e13327. Epub 2022 May 3.

Department of Neurology, Seoul Hospital Ewha Womans University College of Medicine, Seoul, Republic of Korea.

Background: Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor, is a tumor necrosis factor receptor superfamily component. There is an established relationship between OPG and cardiovascular disease. We hypothesized that plasma OPG levels are associated with functional outcomes in acute ischemic stroke patients who have undergone endovascular thrombectomy (EVT).

Methods: From April 2014 through December 2020, a total of 360 acute ischemic stroke patients who underwent EVT were prospectively included in this retrospective observational study. Plasma OPG was measured after fasting for 12 postoperative hours after EVT. A modified Rankin Scale (mRS) was used to assess functional outcomes 3 months after index stroke occurrence. Univariate and multivariate binary logistic regression and ordinal logistic regression analyses were performed to investigate the association of plasma OPG levels with poor functional outcomes.

Results: Overall, 145 (40.2%) patients had poor (mRS > 2) outcomes. The mean ± standard deviation plasma OPG level was 200.2 ± 74.4 pg/mL. Multivariate analysis after adjusting for sex, body mass index, and variables with  < 0.1 in the preceding univariate analysis revealed high plasma OPG levels were independently associated with poor functional outcomes (highest tertile vs. lowest tertile of OPG; odds ratios (OR) 2.121, 95% confidence interval (CI) [1.089-4.191],  = 0.037 in binary logistic regression, OR 2.102, 95% CI [1.301-3.412],  = 0.002 in ordinal logistic regression analysis).

Conclusions: This study demonstrated that higher plasma OPG levels were associated with poor functional outcomes in acute ischemic stroke patients who underwent EVT.
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http://dx.doi.org/10.7717/peerj.13327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074858PMC
May 2022

Wide Phenotypic Spectrum of PNMHH Patients With p.R941L Mutation in .

J Clin Neurol 2022 Mar;18(2):238-240

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3988/jcn.2022.18.2.238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926759PMC
March 2022

Idebenone Regulates Aβ and LPS-Induced Neurogliosis and Cognitive Function Through Inhibition of NLRP3 Inflammasome/IL-1β Axis Activation.

Front Immunol 2022 10;13:749336. Epub 2022 Feb 10.

Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Daegu, South Korea.

Idebenone is an analogue of coenzyme Q10, an electron donor in the mitochondrial electron transport chain, and thus may function as an antioxidant to facilitate mitochondrial function. However, whether idebenone modulates LPS- and Aβ-mediated neuroinflammatory responses and cognitive function is unknown. The present study explored the effects of idebenone on LPS- or Aβ-mediated neuroinflammation, learning and memory and the underlying molecular mechanisms in wild-type (WT) mice and 5xFAD mice, a mouse model of Alzheimer's disease (AD). In male and female WT mice, idebenone upregulated neuroprotective NRF2 expression, rescued LPS-induced spatial and recognition memory impairments, and reduced NLRP3 priming and subsequent neuroinflammation. Moreover, idebenone downregulated LPS-mediated neurogliosis, reactive oxygen species (ROS) levels, and mitochondrial function in BV2 microglial cells and primary astrocytes by inhibiting NLRP3 inflammasome activation. In 5xFAD mice, idebenone increased neuroprotective NRF2 expression and improved amyloid beta (Aβ)-induced cognitive dysfunction. Idebenone downregulated Aβ-mediated gliosis and proinflammatory cytokine levels in 5xFAD mice by modulating the vicious NLRP3/caspase-1/IL-1β neuroinflammation cycle. Taken together, our results suggest that idebenone targets neuroglial NLRP3 inflammasome activation and therefore may have neuroprotective effects and inhibit the pathological progression of neuroinflammation-related diseases.
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http://dx.doi.org/10.3389/fimmu.2022.749336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866241PMC
April 2022

Fatty acid synthetase expression in triple-negative breast cancer.

J Pathol Transl Med 2022 Mar 21;56(2):73-80. Epub 2022 Jan 21.

Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Background: Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism-related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC.

Methods: Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0-1+ FASN staining were grouped as low-grade FASN and patients with 2-3+ FASN staining as high-grade FASN.

Results: FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups.

Conclusions: We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.
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http://dx.doi.org/10.4132/jptm.2021.10.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935000PMC
March 2022

Practical Consideration of Factor Analysis for the Assessment of Construct Validity.

J Korean Acad Nurs 2021 12;51(6):643-647

School of Nursing, Soonchunhyang University, Cheonan, Korea.

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http://dx.doi.org/10.4040/jkan.51601DOI Listing
December 2021

Combined treatment with anti-HER2/neu and anti-4-1BB monoclonal antibodies induces a synergistic antitumor effect but requires dose optimization to maintain immune memory for protection from lethal rechallenge.

Cancer Immunol Immunother 2022 Apr 6;71(4):967-978. Epub 2022 Jan 6.

Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, 47392, Republic of Korea.

Human epidermal growth factor receptor type 2 (HER2)-positive breast cancer that is treated with anti-HER2/neu monoclonal antibody (mAb) is not free from late recurrences. Addition of anti-4-1BB mAb to anti-HER2/neu mAb has been demonstrated to strengthen the cytotoxic antitumor response. Our study expands on this by revealing the influence of anti-4-1BB mAb addition on the immune memory of anti-HER2/neu mAb. We designed murine breast cancer models by implanting TUBO and TUBO-P2J cell lines in mice, which were then treated with anti-HER2/neu and/or anti-4-1BB mAb. After complete surgical and/or chemical regression of the tumor, the mice were rechallenged with a second injection of cancer cells. Notably, anti-HER2/neu and anti-4-1BB mAb combination therapy had a synergistic antitumor effect at the initial treatment. However, the combination therapy did not evoke immune memory, allowing the tumors to thrive at rechallenge with reduced CD44 expression in CD8 T cells. Immune memory was also impaired when anti-4-1BB mAb was administered to naive CD8 T cells but was sustained when this was administered to activated CD8 T cells. In an attempt to resist the loss of immune memory, we controlled the dose of anti-4-1BB mAb to optimize the stimulation of activated CD8 T cells. Immune memory was achieved with the dose regulation of anti-4-1BB mAb to 1 mg/kg in our model. Our study demonstrates the importance in understanding the adaptive immune mechanism of anti-HER2/neu and anti-4-1BB mAb combination therapy and suggests a dose optimization strategy is necessary to ensure development of successful immune memory.
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http://dx.doi.org/10.1007/s00262-021-03120-1DOI Listing
April 2022

Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme.

Int J Oncol 2022 01 16;60(1). Epub 2021 Dec 16.

Department of Microbiology and Immunology, College of Medicine, Inje University, Busan 47392, Republic of Korea.

Myeloid cell leukemia sequence 1 (MCL‑1), an anti‑apoptotic B‑cell lymphoma 2 (BCL‑2) family molecule frequently amplified in various human cancer cells, is known to be critical for cancer cell survival. MCL‑1 has been recognized as a target molecule for cancer treatment. While various agents have emerged as potential MCL‑1 blockers, the present study presented acriflavine (ACF) as a novel MCL‑1 inhibitor in triple‑negative breast cancer (TNBC). Further evaluation of its treatment potential on lung adenocarcinoma and glioblastoma multiforme (GBM) was also investigated. The anticancer effect of ACF on TNBC cells was demonstrated when MDA‑MB‑231 and HS578T cells were treated with ACF. ACF significantly induced typical intrinsic apoptosis in TNBCs in a dose‑ and time‑dependent manner via MCL‑1 downregulation. MCL‑1 downregulation by ACF treatment was revealed at each phase of protein expression. Initially, transcriptional regulation via reverse transcription‑quantitative PCR was validated. Then, post‑translational regulation was explained by utilizing an inhibitor against protein biosynthesis and proteasome. Lastly, immunoprecipitation of ubiquitinated MCL‑1 confirmed the post‑translational downregulation of MCL‑1. In addition, the synergistic treatment efficacy of ACF with the well‑known MCL‑1 inhibitor ABT‑263 against the TNBC cells was explored [combination index (CI)<1]. Conjointly, the anticancer effect of ACF was assessed in GBM (U87, U251 and U343), and lung cancer (A549 and NCI‑H69) cell lines as well, using immunoblotting, cytotoxicity assay and FACS. The effect of the combination treatment using ACF and ABT‑263 was estimated in GBM (U87, U343 and U251), and non‑small cell lung cancer (A549) cells likewise. The present study suggested a novel MCL‑1 inhibitory function of ACF and the synergistic antitumor effect with ABT‑263.
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http://dx.doi.org/10.3892/ijo.2021.5292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698747PMC
January 2022

Variants of aminoacyl-tRNA synthetase genes in Charcot-Marie-Tooth disease: A Korean cohort study.

J Peripher Nerv Syst 2022 03 1;27(1):38-49. Epub 2021 Dec 1.

Department of Biological Sciences, Kongju National University, Gongju, South Korea.

Charcot-Marie-Tooth disease (CMT) and related diseases are a genetically and clinically heterogeneous group of peripheral neuropathies. Particularly, mutations in several aminoacyl-tRNA synthetase (ARS) genes have been reported to cause axonal CMT (CMT2) or distal hereditary motor neuropathy (dHMN). However, the common pathogenesis among CMT subtypes by different ARS gene defects is not well understood. This study was performed to investigate ARS gene mutations in a CMT cohort of 710 Korean families. Whole-exome sequencing was applied to 710 CMT patients who were negative for PMP22 duplication. We identified 12 disease-causing variants (from 13 families) in GARS1, AARS1, HARS1, WARS1, and YARS1 genes. Seven variants were determined to be novel. The frequency of overall ARS gene mutations was 1.22% among all independent patients diagnosed with CMT and 1.83% in patients negative for PMP22 duplication. WARS1 mutations have been reported to cause dHMN; however, in our patients with WARS1 variants, CMT was associated with sensory involvement. We analyzed genotype-phenotype correlations and expanded the phenotypic spectrum of patients with CMT possessing ARS gene variants. We also characterized clinical phenotypes according to ARS genes. This study will be useful for performing exact molecular and clinical diagnoses and providing reference data for other population studies.
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http://dx.doi.org/10.1111/jns.12476DOI Listing
March 2022

The Anti-diabetic Drug Gliquidone Modulates Lipopolysaccharide-Mediated Microglial Neuroinflammatory Responses by Inhibiting the NLRP3 Inflammasome.

Front Aging Neurosci 2021 29;13:754123. Epub 2021 Oct 29.

Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Daegu, South Korea.

The sulfonylurea drug gliquidone is FDA approved for the treatment of type 2 diabetes. Binding of gliquidone to ATP-sensitive potassium channels (SUR1, Kir6 subunit) in pancreatic β-cells increases insulin release to regulate blood glucose levels. Diabetes has been associated with increased levels of neuroinflammation, and therefore the potential effects of gliquidone on micro- and astroglial neuroinflammatory responses in the brain are of interest. Here, we found that gliquidone suppressed LPS-mediated microgliosis, microglial hypertrophy, and proinflammatory cytokine COX-2 and IL-6 levels in wild-type mice, with smaller effects on astrogliosis. Importantly, gliquidone downregulated the LPS-induced microglial NLRP3 inflammasome and peripheral inflammation in wild-type mice. An investigation of the molecular mechanism of the effects of gliquidone on LPS-stimulated proinflammatory responses showed that in BV2 microglial cells, gliquidone significantly decreased LPS-induced proinflammatory cytokine levels and inhibited ERK/STAT3/NF-κB phosphorylation by altering NLRP3 inflammasome activation. In primary astrocytes, gliquidone selectively affected LPS-mediated proinflammatory cytokine expression and decreased STAT3/NF-κB signaling in an NLRP3-independent manner. These results indicate that gliquidone differentially modulates LPS-induced microglial and astroglial neuroinflammation in BV2 microglial cells, primary astrocytes, and a model of neuroinflammatory disease.
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http://dx.doi.org/10.3389/fnagi.2021.754123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8587901PMC
October 2021

Plasma osteoprotegerin levels are associated with the presence and burden of cerebral small vessel disease in patients with acute ischemic stroke.

Clin Neurol Neurosurg 2021 11 28;210:107010. Epub 2021 Oct 28.

Department of Neurology, Seoul Hospital Ewha Womans University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background And Purpose: Osteoprotegerin (OPG) is a component of the tumor necrosis factor receptor superfamily. Several studies have shown a relationship between OPG and cardiovascular diseases. We hypothesized that there is a relationship between plasma OPG levels and cerebral small vessel disease (SVD).

Methods: Patients diagnosed with their first cerebral ischemic infarction between April 2014 and March 2017 were enrolled. All the enrolled patients were evaluated through the hospital stroke protocol, including routine blood tests, brain imaging, and measuring the plasma OPG levels. The presence and burden of cerebral SVD [cerebral microbleeds (CMBs), asymptomatic lacunar infarction (ALI), high-grade perivascular space (HPVS), high-grade white matter hyperintensity (HWMH)], and total SVD score were assessed through brain magnetic resonance imaging.

Results: Of the 270 patients included in our study, 158 (58.5%) were men. The mean age of the patients was 63.8 ± 11.6 years. In multivariable analysis, plasma OPG levels were positively associated with the presence and burden of each cerebral SVD. The odds ratios (OR) of CMBs, ALI, HPVS, and HWMH for the association of OPG per standard deviation (SD) increase were 1.58 [95% confidence interval (CI), 1.09-2.27], 1.40 (95% CI, 1.04-1.88), 1.88 (95% CI, 1.27-2.78), and 1.47 (95% CI, 1.04-2.08), respectively. Plasma OPG levels were positively correlated with total SVD score (beta = 0.211, standard error = 0.061, p-value = 0.009, R = 0.275).

Conclusions: Plasma OPG levels correlate with the presence and burden of cerebral SVD in patients with acute ischemic stroke.
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http://dx.doi.org/10.1016/j.clineuro.2021.107010DOI Listing
November 2021

Mobile web-based self-management program for breast cancer patients with chemotherapy-induced amenorrhoea: A quasi-experimental study.

Nurs Open 2022 01 30;9(1):655-665. Epub 2021 Oct 30.

College of Nursing, Research Institute of Nursing Science, Ajou University, Suwon, South Korea.

Aim: The aim of this study was to examine the effects of a mobile web-based self-management program on menopausal symptoms, self-efficacy and quality of life in breast cancer patients with chemotherapy-induced amenorrhoea.

Design: A quasi-experimental pretest-posttest design with repeated measures.

Methods: The study was carried out at a university medical centre between October 2017 and September 2018. The intervention group received a 12-week mobile web-based self-management program including education and coaching/support. Multiple instruments were used to measure menopausal symptoms, self-efficacy, and quality of life at pre-test, after the intervention (post-test), and 3 months post-intervention (follow-up test). Repeated measure ANOVA was used to analyse the data.

Results: In the intervention group, menopausal symptoms were significantly improved compared to the control group at the follow-up test. In the follow-up test, the intervention group's self-efficacy and quality of life were significantly improved, whereas that of the control group was decreased.
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http://dx.doi.org/10.1002/nop2.1113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685845PMC
January 2022

Determinants of quality of life in women immediately following the completion of primary treatment of breast cancer: A cross-sectional study.

PLoS One 2021 15;16(10):e0258447. Epub 2021 Oct 15.

College of Nursing Research Institute of Nursing Science, Ajou University, Suwon, South Korea.

Backgrounds: Many breast cancer patients experience significant distress immediately following the completion of primary treatment. Women who report low levels of quality of life (QOL) early in this phase of transitional survivorship tend to experience diminished long-term adjustment. However, since most of the prior studies on survivors were conducted on patients at various times, studies on QOL of women during the end of primary treatment have been insufficient. This study aimed to identify determinants of QOL in women with breast cancer immediately following the completion of treatment.

Methods: A cross-sectional study was conducted on 140 disease-free breast cancer patients who had completed therapy in the past 1 month at university hospitals. Functional Assessment of Cancer Therapy-Breast (FACT-B), Memorial Symptom Assessment Scale-Short Form (MSAS-SF), Self-Efficacy Scale for Self-Management of Breast Cancer (SESSM-B), and Interpersonal Support Evaluation List-12 (ISEL-12) scales were used to assess predictors and QOL. The data were analyzed using the Pearson correlation, t-test, ANOVA, and hierarchical multiple regression.

Results: The mean score of QOL for breast cancer survivors was 97.23 (±20.01). Chemotherapy and perceived economic status were significantly associated with QOL in terms of sociodemographic and disease/treatment-related characteristics. Physical and psychological symptoms and social support had a significant association with QOL. The regression analyses showed that physical and psychological symptoms and belonging support were statistically significant in predicting the QOL of breast cancer survivors.

Conclusions: The variables of symptom experience and social support must be acknowledged when improving women's QOL immediately after their completion of primary breast cancer treatment. Greater focus on the reduction of symptom distress and increasing a sense of belonging could improve QOL among breast cancer survivors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258447PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519416PMC
December 2021

Donepezil Regulates LPS and Aβ-Stimulated Neuroinflammation through MAPK/NLRP3 Inflammasome/STAT3 Signaling.

Int J Mol Sci 2021 Sep 30;22(19). Epub 2021 Sep 30.

Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, Korea.

The acetylcholinesterase inhibitors donepezil and rivastigmine have been used as therapeutic drugs for Alzheimer's disease (AD), but their effects on LPS- and Aβ-induced neuroinflammatory responses and the underlying molecular pathways have not been studied in detail in vitro and in vivo. In the present study, we found that 10 or 50 μM donepezil significantly decreased the LPS-induced increases in the mRNA levels of a number of proinflammatory cytokines in BV2 microglial cells, whereas 50 μM rivastigmine significantly diminished only LPS-stimulated IL-6 mRNA levels. In subsequent experiments in primary astrocytes, donepezil suppressed only LPS-stimulated iNOS mRNA levels. To identify the molecular mechanisms by which donepezil regulates LPS-induced neuroinflammation, we examined whether donepezil alters LPS-stimulated proinflammatory responses by modulating LPS-induced downstream signaling and the NLRP3 inflammasome. Importantly, we found that donepezil suppressed LPS-induced AKT/MAPK signaling, the NLRP3 inflammasome, and transcription factor NF-kB/STAT3 phosphorylation to reduce neuroinflammatory responses. In LPS-treated wild-type mice, a model of neuroinflammatory disease, donepezil significantly attenuated LPS-induced microglial activation, microglial density/morphology, and proinflammatory cytokine COX-2 and IL-6 levels. In a mouse model of AD (5xFAD mice), donepezil significantly reduced Aβ-induced microglial and astrocytic activation, density, and morphology. Taken together, our findings indicate that donepezil significantly downregulates LPS- and Aβ-evoked neuroinflammatory responses in vitro and in vivo and may be a therapeutic agent for neuroinflammation-associated diseases such as AD.
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http://dx.doi.org/10.3390/ijms221910637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508964PMC
September 2021

Idebenone Decreases Aβ Pathology by Modulating RAGE/Caspase-3 Signaling and the Aβ Degradation Enzyme NEP in a Mouse Model of AD.

Biology (Basel) 2021 Sep 19;10(9). Epub 2021 Sep 19.

Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61 Cheomdan-ro, Dong-gu, Daegu 41068, Korea.

The coenzyme Q10 analogue idebenone is an FDA-approved antioxidant that can cross the blood-brain barrier (BBB). The effects of idebenone on the pathology of Alzheimer's disease (AD) and the underlying molecular mechanisms have not been comprehensively investigated. Here, we examined the impact of idebenone treatment on AD pathology in 5xFAD mice, a model of AD. Idebenone significantly downregulated Aβ plaque number via multi-directional pathways in this model. Specifically, idebenone reduced the RAGE/caspase-3 signaling pathway and increased levels of the Aβ degradation enzyme NEP and α-secretase ADAM17 in 5xFAD mice. Importantly, idebenone significantly suppressed tau kinase p-GSK3β levels, thereby inhibiting tau hyperphosphorylation at Thr231 and total tau levels in 5xFAD mice. Taken together, the present study indicates that idebenone modulates amyloidopathy and tauopathy in 5xFAD mice, suggesting therapeutic potential for AD.
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http://dx.doi.org/10.3390/biology10090938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471964PMC
September 2021

Effect of pyroligneous acid on soil urease, amidase, and nitrogen use efficiency by Chinese cabbage (Brassica campestris var. Pekinensis).

Environ Pollut 2021 Dec 8;291:118132. Epub 2021 Sep 8.

Chungbuk National University, Cheongju, Chungbuk, 28644, South Korea. Electronic address:

Urea is one of the most commonly used nitrogen fertilizers in agricultural soil and is easily decomposed by soil urease resulting in ammonium release. The produced ammonium can be volatilized or converted to nitrate, which is susceptible to leaching, leading to groundwater contamination unless used by plants. Hence, it is important to control the release of nitrogen from the urea. Pyroligneous acid inhibited the urease activity and decreased ammonium release up to 80% compared to the control. Amidase including asparaginase and glutaminase is an enzyme that catalyzes hydrolysis of amide group, similar to urease. Therefore, the effect of pyroligneous acid on the inhibition of soil amidase was also tested and the results showed that pyroligneous acid competitively inhibited asparaginase while glutaminase was not inhibited. However, inhibitory effect of pyroligneous acid on asparaginase was negligible compared to the urease. The application of pyroligneous acid with a smaller amount of urea for controlled nitrogen release during Chinese cabbage growth showed that dry biomass and nutrient contents of Chinese cabbage were similar to the case of the conventional urea application. The nitrogen utilization efficiency (NUE) was highest for 33% less amount of urea supply with pyroligneous acid (2.21) compared to conventional treatment (1.81). Consequently, the use of pyroligneous acid with urea enhances nitrogen use efficiency while also protecting environments from non-point source contamination.
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http://dx.doi.org/10.1016/j.envpol.2021.118132DOI Listing
December 2021

Information and General Guidance for Healthcare Professionals in the Fourth Wave of COVID-19.

J Korean Acad Nurs 2021 Aug;51(4):395-407

College of Nursing · Research Institute of Nursing Science, Ajou University, Suwon, Korea.

The COVID-19 curve seesawed and reached the fourth pandemic in July 2021. Since the first three waves, the focus has been on achieving herd immunity through vaccination while a lot of manpower is used for quarantine. However, we have not been able to prevent the fourth wave. The causes are thought to be related to people who doubt the safety of the vaccine and refuse it or violate quarantine guidelines such as social distancing. This study examined guidelines for preventing and controlling COVID-19, the accuracy of vaccination-related information, and described quarantine measures including for those who completed vaccination. In conclusion, prevention and vaccination are the most effective countermeasures against COVID-19. We recommend people vaccination with self-quarantine. Also, it is necessary to make large investments to protect and support nurses in future pandemics.
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http://dx.doi.org/10.4040/jkan.21137DOI Listing
August 2021

Incidence and Risk Factors of Cardio-Cerebrovascular Disease in Korean Menopausal Women: A Retrospective Observational Study using the Korean Genome and Epidemiology Study data.

Asian Nurs Res (Korean Soc Nurs Sci) 2021 Oct 23;15(4):265-271. Epub 2021 Aug 23.

College of Nursing·Research Institute of Nursing Science, Ajou University, Suwon, Republic of Korea. Electronic address:

Purpose: Cardio-cerebrovascular diseases constitute the most common and fatal disease among menopausal women. However, the risk of cardio-cerebrovascular diseases in menopausal women compared to men has been underestimated, with insufficient related studies. Therefore, we examined the incidence and risk factors of cardio-cerebrovascular diseases among Korean menopausal women.

Methods: A retrospective observational study design with secondary analysis was conducted using data from the Korean Genome and Epidemiology Study survey. We used the study's data of 1,197 menopausal women, aged 40-64 years, who did not have cardio-cerebrovascular diseases at baseline and their related data from the biennial follow-ups over 14 years. Cardio-cerebrovascular diseases were defined as hypertension, coronary artery disease, or stroke. The incidence of cardio-cerebrovascular diseases was calculated per person-years, and multivariate Cox proportional hazards models were used to determine the predictors of cardio-cerebrovascular diseases during the follow-up period.

Results: Of the 1,197 cases, 264 were early or surgical menopausal women. The overall incidence of cardio-cerebrovascular diseases was 18.75 per 1,000 person-years. Early or surgical menopause (HR = 4.32, p < .001), along with family history of cardiovascular disease (HR = 1.87, p = .024), elevated blood pressure (HR = 1.79, p < .001), abdominal obesity (HR = 1.37, p = .046), or duration of menopause at the same age (HR = 1.01, p = .001), were strong predictors of cardio-cerebrovascular diseases.

Conclusion: Based on the results of this study, it is necessary to identify and closely monitor women with early or surgical menopause for cardiovascular and cerebrovascular diseases prevention. Also, prevention of cardio-cerebrovascular diseases through blood pressure and abdominal obesity management is vital for menopausal women.
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http://dx.doi.org/10.1016/j.anr.2021.08.002DOI Listing
October 2021

Tetraspanin 7 regulates osteoclast function through association with the RANK/αvβ3 integrin complex.

J Cell Physiol 2022 01 18;237(1):846-855. Epub 2021 Aug 18.

Department of Life Science, Ewha Womans University, Seoul, South Korea.

Actin rings are unique structures that facilitate the attachment of osteoclasts to the bone matrix during bone resorption. Previous studies have shown that tetraspanin7 (TSPAN7) plays an important role in the reorganization of the cytoskeleton necessary for the bone-resorbing activity of osteoclasts. However, questions remain as to the mechanisms by which TSPAN7 regulates this cytoskeletal rearrangement. In this study, we investigated the roles of TSPAN7 in osteoclasts by deleting the Tm4sf2 gene in mice, which encodes TSPAN7. The Tm4sf2 global knockout model showed protective effects on pathological bone loss, but no discernible changes in bone phenotypes under physiological conditions. In vitro study revealed that ablation of Tm4sf2 caused significant defects in integrin-mediated actin ring formation, thereby leading to significantly decreased bone resorption. Additionally, we demonstrated an association between TSPAN7 and the receptor activator of nuclear factor-кB/αvβ3 integrin. Overall, our findings suggest that TSPAN7 acts as a novel modulator regulating the bone-resorbing function of osteoclasts.
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http://dx.doi.org/10.1002/jcp.30559DOI Listing
January 2022

Reliability and validity of the Korean version of the MacNew heart disease Health-related Quality of Life questionnaire.

Health Qual Life Outcomes 2021 Aug 14;19(1):196. Epub 2021 Aug 14.

College of Nursing·Research Institute of Nursing Science, Ajou University, 164, World cup-Ro, Yeongtong-Gu, Suwon, 16499, Korea.

Background: Myocardial infarction and unstable angina are prevalent in Korea. The MacNew Heart Disease health-related quality of life questionnaire is a widely used patient-reported outcome measure for patients with heart disease in several countries. In this study, we tested the validity and reliability of the Korean version of the MacNew (K-MacNew).

Methods: Participants were 200 patients who had experienced unstable angina or myocardial infarction, and were recruited from a tertiary hospital in Korea. The K-MacNew was developed using forward-backward translation techniques. Construct validity (including discriminative validity), concurrent validity, and internal consistency reliability of the K-MacNew were assessed. Discriminative validity was assessed by examining the between-group differences in the K-MacNew scores according to functional capacity, anxiety, and depression levels. Concurrent validity was examined by correlating the K-MacNew dimensions with the physical and mental health domains of the 36-item Short Form Health Survey Instrument (SF-36).

Results: Factor analysis results of the K-MacNew demonstrated a three-factor structure (emotional, physical, and social) that explained 57.92% of the variance. Significant differences in the K-MacNew scores were observed according to patients' functional capacity, anxiety, and depression levels. The SF-36 physical health domain score showed a moderate positive correlation with the physical dimension score of the K-MacNew (r = 0.517, P < 0.001), and the SF-36 mental health domain score showed a strong positive correlation with the emotional dimension of K-MacNew (r = 0.745, P < 0.001). The K-MacNew showed good internal consistency, with a Cronbach's α of 0.947 for the global scale.

Conclusion: The K-MacNew demonstrated good reliability and validity for use as a patient-reported outcome measure and is ready for the assessment of the health-related quality of life of patients with coronary artery disease in Korea. To establish the clinical validity of the K-MacNew, additional studies should be conducted to verify the validity and reliability of the K-MacNew in a number of participants, including those with various types of coronary artery disease.
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http://dx.doi.org/10.1186/s12955-021-01832-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364118PMC
August 2021

A phenomenological study on the experiences of patient transfer from the intensive care unit to general wards.

PLoS One 2021 7;16(7):e0254316. Epub 2021 Jul 7.

College of Nursing Research Institute of Nursing Science, Ajou University, Suwon, South Korea.

Objectives: This study aimed to derive an in-depth understanding of the transfer experience of intensive care unit (ICU) patients in South Korea through a phenomenological analysis.

Methods: Participants were 15 adult patients who were admitted to a medical or surgical ICU at a university hospital for more than 48 hours before being transferred to a general ward. Data were collected three to five days after their transfer to the general ward from January to December 2017 through individual in-depth interviews and were analyzed using Colaizzi's phenomenological data analysis method, phenomenological reduction, intersubjective reduction, and hermeneutic circle. Data analysis yielded eight themes and four theme clusters related to the unique experiences of domestic ICU patients in the process of transfer to the general ward.

Results: The four main themes of the patients' transfer experiences were "hope amid despair," "gratitude for being alive," "recovery from suffering," and "seeking a return to normality."

Conclusion: Our findings expand the realistic and holistic understanding from the patient's perspective. This study's findings can contribute to the development of appropriate nursing interventions that can support preparation and adaptation to the transfer of ICU patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254316PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263304PMC
November 2021

Novel homozygous mutations in Pakistani families with Charcot-Marie-Tooth disease.

BMC Med Genomics 2021 06 30;14(1):174. Epub 2021 Jun 30.

Department of Biological Sciences, Kongju National University, 56 Gongjudaehakro, Gongju, 32588, Korea.

Background: Charcot-Marie-Tooth disease (CMT) is a group of genetically and clinically heterogeneous peripheral nervous system disorders. Few studies have identified genetic causes of CMT in the Pakistani patients.

Methods: This study was performed to identify pathogenic mutations in five consanguineous Pakistani CMT families negative for PMP22 duplication. Genomic screening was performed by application of whole exome sequencing.

Results: We identified five pathogenic or likely pathogenic homozygous mutations in four genes: c.2599C > T (p.Gln867*) and c.3650G > A (p.Gly1217Asp) in SH3TC2, c.19C > T (p.Arg7*) in HK1, c.247delG (p.Gly83Alafs*44) in REEP1, and c.334G > A (p.Val112Met) in MFN2. These mutations have not been reported in CMT patients. Mutations in SH3TC2, HK1, REEP1, and MFN2 have been reported to be associated with CMT4C, CMT4G, dHMN5B (DSMA5B), and CMT2A, respectively. The genotype-phenotype correlations were confirmed in all the examined families. We also confirmed that both alleles from the homozygous variants originated from a single ancestor using homozygosity mapping.

Conclusions: This study found five novel mutations as the underlying causes of CMT. Pathogenic mutations in SH3TC2, HK1, and REEP1 have been reported rarely in other populations, suggesting ethnic-specific distribution. This study would be useful for the exact molecular diagnosis and treatment of CMT in Pakistani patients.
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http://dx.doi.org/10.1186/s12920-021-01019-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247155PMC
June 2021

Kinesin-1-dependent transport of the βPIX/GIT complex in neuronal cells.

BMB Rep 2021 Jul;54(7):380-385

Departments of Biochemistry, College of Medicine, and Medical Research Center, Chungbuk National University, Cheongju 28644, Korea.

Proper targeting of the βPAK-interacting exchange factor (βPIX)/G protein-coupled receptor kinase-interacting target protein (GIT) complex into distinct cellular compartments is essential for its diverse functions including neurite extension and synaptogenesis. However, the mechanism for translocation of this complex is still unknown. In the present study, we reported that the conventional kinesin, called kinesin-1, can transport the βPIX/GIT complex. Additionally, βPIX bind to KIF5A, a neuronal isoform of kinesin-1 heavy chain, but not KIF1 and KIF3. Mapping analysis revealed that the tail of KIF5s and LZ domain of βPIX were the respective binding domains. Silencing KIF5A or the expression of a variety of mutant forms of KIF5A inhibited βPIX targeting the neurite tips in PC12 cells. Furthermore, truncated mutants of βPIX without LZ domain did not interact with KIF5A, and were unable to target the neurite tips in PC12 cells. These results defined kinesin-1 as a motor protein of βPIX, and may provide new insights into βPIX/GIT complex-dependent neuronal pathophysiology. [BMB Reports 2021; 54(7): 380-385].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328822PMC
July 2021

Sorafenib Modulates the LPS- and Aβ-Induced Neuroinflammatory Response in Cells, Wild-Type Mice, and 5xFAD Mice.

Front Immunol 2021 27;12:684344. Epub 2021 May 27.

Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Daegu, South Korea.

Sorafenib is FDA-approved for the treatment of primary kidney or liver cancer, but its ability to inhibit many types of kinases suggests it may have potential for treating other diseases. Here, the effects of sorafenib on neuroinflammatory responses and and the underlying mechanisms were assessed. Sorafenib reduced the induction of mRNA levels of the proinflammatory cytokines COX-2 and IL-1β by LPS in BV2 microglial cells, but in primary astrocytes, only COX-2 mRNA levels were altered by sorafenib. Interestingly, sorafenib altered the LPS-mediated neuroinflammatory response in BV2 microglial cells by modulating AKT/P38-linked STAT3/NF-kB signaling pathways. In LPS-stimulated wild-type mice, sorafenib administration suppressed microglial/astroglial kinetics and morphological changes and COX-2 mRNA levels by decreasing AKT phosphorylation in the brain. In 5xFAD mice (an Alzheimer's disease model), sorafenib treatment daily for 3 days significantly reduced astrogliosis but not microgliosis. Thus, sorafenib may have therapeutic potential for suppressing neuroinflammatory responses in the brain.
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http://dx.doi.org/10.3389/fimmu.2021.684344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190398PMC
October 2021

The complete chloroplast genome of cv. Hwang-Moran (Paeoniaceae).

Mitochondrial DNA B Resour 2021 Jan 27;6(1):280-281. Epub 2021 Jan 27.

Department of Industrial Plant Science and Technology, Chungbuk National University, Cheongju, South Korea.

The complete chloroplast genome of cv. Hwang-Moran (PHM), a yellow flowering tree peony, was assembled and characterized from high-throughput next-generation sequencing data. The total length of the circular PHM chloroplast genome was 152,519 bp, including a large single-copy (LSC) region of 84,214 bp, a small single-copy (SSC) region of 17,026 bp, and a pair of inverted repeat regions (IRs) of 25,640 bp. The entire chloroplast genome contained 111 genes, including 77 protein-coding genes, 30 tRNAs, and four rRNAs. A phylogenetic tree constructed using the PHM and related chloroplast genome sequences revealed its close taxonomic relationship with within the genus .
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http://dx.doi.org/10.1080/23802359.2020.1860721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850342PMC
January 2021

Enlightening the Immune Mechanism of the Abscopal Effect in a Murine HCC Model and Overcoming the Late Resistance With Anti-PD-L1.

Int J Radiat Oncol Biol Phys 2021 06 29;110(2):510-520. Epub 2020 Dec 29.

Department of Microbiology, College of Medicine, Inje University, Busan, Republic of Korea. Electronic address:

Purpose: The establishment of a preclinical model of the abscopal effect on hepatocellular carcinoma (HCC) and evaluation of whether the hypofractionated radiation therapy (RT) multitumor Hepa1-6 mouse HCC model could be used to suppress nonradiated tumor mass was performed in this study.

Methods And Materials: Hepa1-6 mouse liver cancer cell lines were used to form tumors. Immunogenicity was analyzed using ELISpot and immune cell labeled antibody. Interferon (IFN) β expression was confirmed through polymerase chain reaction.

Results: After investigation, the intratumoral transcription of type Ⅰ IFN increased by 2-fold. The antitumor immune response to Hepa 1-6 cells induced by radiation was increased. Moreover, the influx of activated CD8 T cells was increased in nonirradiated tumors. The number of dendritic cells and activation status were evaluated by flow cytometry on the second day after irradiation. Flow cytometry revealed a significantly increased dendritic cell population expressing the CD11c molecule in tumor-draining lymph nodes. Furthermore, because irradiation leads to adaptation of immune resistance of tumor cells against RT, we sought to elucidate a potent tool to overcome the resistance and confirm the ability of PD-L1 antibody to survive late RT resistance.

Conclusions: The immunologic mechanism of the abscopal effect was revealed and the application of PD-L1 inhibitor successfully performed as a breakthrough in late RT resistance in the Hepa1-6 tumor model.
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http://dx.doi.org/10.1016/j.ijrobp.2020.12.031DOI Listing
June 2021

Aging effects on fractionation and speciation of redox-sensitive metals in artificially contaminated soil.

Chemosphere 2021 Jan 9;263:127931. Epub 2020 Aug 9.

Geologic Environment Division, Korea Institute of Geoscience and Mineral Resources, Daejeon 34132, Republic of Korea.

Artificially contaminated soil is often used in laboratory experiments as a substitute for actual field contaminated soils. In the preparation and use of laboratory contaminated soils, questions remain as to how much and how long metals remain in labile form and in their oxidation state during the contamination process. Therefore, the objectives of this study were to determine if the speciation of added contaminants can be retained in the original form and to observe the change in lability of each element with aging time. In this study, natural soil was artificially polluted with five redox-sensitive toxic elements in their oxidized or reduced forms, i.e., As(III)/As(V), Sb(III)/Sb(V), Cr(III)/Cr(VI), Mo(VI), and W(V). Metal distribution was measured in progressive chemical fractionation using sequential extraction methods in contaminated soils after 3, 100, and 300 days of aging. The results indicated that the more strongly bound fraction of metals increased by day 100; whereas the fractions were not significantly different from those in the 300-day-aged soil. Among five metals, the ratio of weakly-bound fractions remained highest in As- and lowest in Cr-contaminated soils. The W(VI)-contaminated soil showed strong sorption without changes in speciation during aging. The oxidized or reduced metal species converged to occur as a single species under given soil conditions, regardless of the initial form of metal used to spike the soil. Both As and Sb existed as their oxidized form while Cr existed as its reduced form. The results of this study may provide a useful and practical guideline for artificial soil contamination.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127931DOI Listing
January 2021

Induces Immunogenic Cell Death and Enhances Antitumor Immunogenic Response in Breast Cancer.

Evid Based Complement Alternat Med 2020 3;2020:9053274. Epub 2020 Sep 3.

Department of Microbiology and Immunology, College of Medicine, Inje University, Busan 47392, Republic of Korea.

has been widely used as a traditional medicine in East Asia. Its effects against breast cancer have been reported previously. However, whether -induced breast cancer cell death is immunogenic remains unelucidated. This study aimed to determine whether ethanolic extracts of (CM-EE) could induce immunogenic cell death (ICD) in breast cancer immunotherapy to improve the efficacy of immune checkpoint inhibitors. Human and mouse breast cancer cells were treated with various concentrations of CM-EE for 72 h, and cytotoxicity was measured using the sulforhodamine B assay. Flow cytometry was used to assess cell death with annexin V/7-AAD staining and measure the surface exposure of damage-associated molecular pattern (DAMP) molecules including calreticulin, HSP70, and HSP90. Western blot for cleaved poly (ADP-ribose) polymerase (PARP) was used to confirm apoptotic cell death. The immunogenicity of CM-EE-induced dead cells was evaluated using the CFSE dilution assay. CM-EE reduced the viability of human (MCF7, MDA-MB-231, HS578T, and SKBR3) and mouse (4T1-neu-HA, TUBO-HA, and TUBO-P2J-HA) breast cancer cells. The IC was 25-50 g/ml in human breast cancer cells and 10-50 g/ml in mouse breast cancer cells at 72 h. CM-EE-treated breast cancer cells were positively stained by annexin V, cleaved PARP, and cleaved caspase 3/7 which were increased upon CM-EE treatment. Surface exposure of DAMP molecules was increased in dose- and time-dependent manners. The CFSE dilution assay revealed that dendritic cells fed with CM-EE-treated breast cancer cells successfully stimulated tumor-specific T cell proliferation without inhibiting DC function and T cell proliferation. The expression of PD-L1 mRNA and protein level was increased in dose-dependent manners. In addition, CM-EE also potentiated the cytotoxic activity of tumor-specific T cells. CM-EE can induce immunogenic and apoptotic cell death in breast cancer cells, and it is a good candidate for cancer immunotherapy and may improve the efficacy of immune checkpoint inhibitors.
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http://dx.doi.org/10.1155/2020/9053274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486645PMC
September 2020

Ivabradine-Induced Torsade de Pointes in Patients with Heart Failure Reduced Ejection Fraction.

Int Heart J 2020 Sep 12;61(5):1044-1048. Epub 2020 Sep 12.

Department of Cardiology, Inha University Hospital Cardiovascular Center.

Ivabradine is a selective inhibitor of the sinoatrial node "funny" current, prolonging the slow diastolic depolarization. As it has the ability to block the heart rate selectively, it is more effective at a faster heart rate. It is recommended for the treatment of heart failure reduced ejection fraction in the presence of beta-blocker therapy for the further reduction of the heart rate. However, previous reports have shown the association of Torsade de pointes (TdP) with concurrent use of ivabradine and drugs resulting in QT prolongation or blockage of the metabolic breakdown of ivabradine. In this article, we report two cases of patients with heart failure reduced ejection fraction who developed TdP after ivabradine use. Our report highlights the need to exercise caution with the administration of ivabradine in the presence of a reduced repolarization reserve, such as QT prolongation or metabolic insufficiency.
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http://dx.doi.org/10.1536/ihj.20-073DOI Listing
September 2020

Analysis of Research Topics and Trends in the Journal of Korean Academy of Nursing to Improve Its International Influence.

J Korean Acad Nurs 2020 Aug;50(4):501-512

College of Nursing Science · East-West Nursing Research Institute, Kyung Hee University, Seoul, Korea.

Purpose: The purpose of this study was to analyze articles published in the Journal of the Korean Academy of Nursing (JKAN) between 2010 and 2019, along with those published in three international nursing journals, to improve JKAN's international reputation.

Methods: The overall characteristics of JKAN's published papers and keywords, study participants, types of nursing interventions and dependent variables, citations, and cited journals were analyzed. Additionally, the keywords and study designs, publication-related characteristics, journal impact factors (JIF), and Eigenfactor scores of International Journal of Nursing Studies (IJNS), International Nursing Review (INR), Nursing & Health Sciences (NHS), and JKAN were analyzed and compared.

Results: Among the four journals, JKAN's score was the lowest in both the journal impact factor and Eigenfactor score. In particular, while the JIF of INR and NHS has been continuously increasing; JKAN's JIF has remained static for almost 10 years. The journals which had cited JKAN and those which JKAN had cited were mainly published in Korean.

Conclusion: JKAN still has a low IF and a low ranking among Social Citation Index (E) journals during the past 10 years, as compared to that of four international journals. To enhance JKAN's status as an international journal, it is necessary to consider publishing it in English and to continuously improve the conditions of other publications.
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http://dx.doi.org/10.4040/jkan.20167DOI Listing
August 2020

The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD.

Cells 2020 08 28;9(9). Epub 2020 Aug 28.

Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, Korea.

Monoamine oxidase (MAO) has been implicated in neuroinflammation, and therapies targeting MAO are of interest for neurodegenerative diseases. The small-molecule drug tranylcypromine, an inhibitor of MAO, is currently used as an antidepressant and in the treatment of cancer. However, whether tranylcypromine can regulate LPS- and/or Aβ-induced neuroinflammation in the brain has not been well-studied. In the present study, we found that tranylcypromine selectively altered LPS-induced proinflammatory cytokine levels in BV2 microglial cells but not primary astrocytes. In addition, tranylcypromine modulated LPS-mediated TLR4/ERK/STAT3 signaling to alter neuroinflammatory responses in BV2 microglial cells. Importantly, tranylcypromine significantly reduced microglial activation as well as proinflammatory cytokine levels in LPS-injected wild-type mice. Moreover, injection of tranylcypromine in 5xFAD mice (a mouse model of AD) significantly decreased microglial activation but had smaller effects on astrocyte activation. Taken together, our results suggest that tranylcypromine can suppress LPS- and Aβ-induced neuroinflammatory responses in vitro and in vivo.
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http://dx.doi.org/10.3390/cells9091982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563969PMC
August 2020
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