Publications by authors named "Jieun Kim"

482 Publications

S1 Brain Connectivity in Carpal Tunnel Syndrome Underlies Median Nerve and Functional Improvement Following Electro-Acupuncture.

Front Neurol 2021 27;12:754670. Epub 2021 Oct 27.

Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States.

Carpal Tunnel Syndrome (CTS) is a median nerve entrapment neuropathy that alters primary somatosensory cortex (S1) organization. While electro-acupuncture (EA), a form of peripheral neuromodulation, has been shown to improve clinical and neurophysiological CTS outcomes, the role of EA-evoked brain response during therapy (within and beyond S1) for improved outcomes is unknown. We investigated S1-associated whole brain fMRI connectivity during both a resting and sustained EA stimulation state in age-matched healthy controls ( = 28) and CTS patients ( = 64), at baseline and after 8 weeks of acupuncture therapy (local, distal, or sham EA). Compared to healthy controls, CTS patients at baseline showed decreased resting state functional connectivity between S1 and thalamic pulvinar nucleus. Increases in S1/pulvinar connectivity strength following verum EA therapy (combined local and distal) were correlated with improvements in median nerve velocity ( = 0.38, = 0.035). During sustained local EA, compared to healthy controls, CTS patients demonstrated increased functional connectivity between S1 and anterior hippocampus (aHipp). Following 8 weeks of local EA therapy, S1/aHipp connectivity significantly decreased and greater decrease was associated with improvement in patients' functional status ( = 0.64, = 0.01) and increased median nerve velocity ( = -0.62, = 0.013). Thus, connectivity between S1 and other brain areas is also disrupted in CTS patients and may be improved following EA therapy. Furthermore, stimulus-evoked fMRI connectivity adds therapy-specific, mechanistic insight to more common resting state connectivity approaches. Specifically, local EA modulates S1 connectivity to sensory and affective processing regions, linked to patient function and median nerve health.
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http://dx.doi.org/10.3389/fneur.2021.754670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578723PMC
October 2021

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

Effect of benzotriazole on oxidative stress response and transcriptional gene expression in Oryzias latipes and Danio rerio embryo.

Comp Biochem Physiol C Toxicol Pharmacol 2021 Oct 28;252:109222. Epub 2021 Oct 28.

Risk Assessment Division, National Institute of Environmental Research, Kyungseo-Dong, Seo-gu, Incheon 22689, Republic of Korea. Electronic address:

Emerging contaminants (EC) such as benzotriazole are being released into the environment in various ways, therefore it is necessary to understand how organisms are affected by EC. In this study, we exposed medaka (Oryzias latipes) and zebrafish (Danio rerio) during their embryonic period (1 day after hatching) to benzotriazole to investigate its effects on oxidative stress (ROS, GSH, GST, SOD, CAT and MDA) and changes in gene expression patterns. In both medaka and zebrafish, the influence of oxidative stress was confirmed through an increased MDA level and changes in the ROS and GSH levels. Antioxidant enzymes such as GST, CAT, and SOD were affected by benzotriazole; however, medaka and zebrafish showed different patterns in the effects by benzotriazole. Results of oxidative stress genes expression showed that medaka had either no influence or had a decrease in the gene expression profile, whereas zebrafish had a statistically significant increase in the expression of some genes. The cyp1a gene expression was increased in both species. However, vtg gene expression was increased only in zebrafish but decreased in medaka, indicating no estrogenic effects in medaka. Apoptosis genes showed changes in expression in both the species but was these changes were not dose-dependent. However, zebrafish caspase-9 gene expression was increased in all of the exposed groups, suggesting the effects on the intrinsic pathway associated with caspase-9. In conclusion, the results indicate that the toxic effects of benzotriazole differ at various levels in the two small fish medaka and zebrafish embryos.
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http://dx.doi.org/10.1016/j.cbpc.2021.109222DOI Listing
October 2021

Genetic Relatedness of 5-Year Isolates of Polymerase Chain Reaction Ribotype 017 Strains in a Hospital.

Antibiotics (Basel) 2021 Oct 9;10(10). Epub 2021 Oct 9.

Department of Internal Medicine, College of Medicine, Hanyang University, Seoul 04763, Korea.

The objective of this study was to analyse the genetic relatedness of polymerase chain reaction ribotype 017 (RT017) strains from patients with hospital-acquired infection (HA-CDI) in a hospital with a high RT017 prevalence. From 2009 to 2013, 200 RT017 strains (26.8%) were collected from 745 HA-CDI patient isolates. They comprised 64 MLVA types, and 197 (98.5%) strains were genetically related to 5 clonal complexes (CCs). The largest cluster, CC-A, included 163 isolates of 40 MLVA types. CC-A accounted for 20% of RT017 strains in 2009 and sharply increased to 94.9% in 2010, 94% in 2011, 86.2% in 2012, and 73.5% in 2013. The other 4 CCs included 20 isolates with 7 MLVA types. The resistance rates of antimicrobials were as follows: clindamycin 100%, moxifloxacin 99%, rifaximin 88.5%, and vancomycin 1%. All isolates were susceptible to metronidazole and piperacillin/tazobactam. Comparing antibiotic resistance among CCs, the geometric mean of the minimum inhibitory concentrations of moxifloxacin, vancomycin, and piperacillin/tazobactam were significantly higher for CC-A isolates than for the other CCs. RT017 clones constantly evolved over the 5 years studied with regard to genetic relatedness. The levels of antibiotic resistance may contribute to the persistence of organisms in the institution.
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http://dx.doi.org/10.3390/antibiotics10101229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532766PMC
October 2021

Investigation of combined treatment of acupuncture and neurofeedback for improving cognitive function in mild neurocognitive disorder: A randomized, assessor-blind, pilot study.

Medicine (Baltimore) 2021 Sep;100(37):e27218

Department of Oriental Neuropsychiatry, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea.

Background: Mild neurocognitive disorder (MND) is an intermediate state that can progress to dementia, and the cognitive reserve of MND is an important task in preventing dementia. Acupuncture and neurofeedback (NF) training have been used to improve cognitive function and treat MND or dementia, but their effectiveness remains controversial. In this trial, we will evaluate the efficacy and safety of combined NF-acupuncture treatment in comparison with single acupuncture treatment.

Methods And Design: This study is a randomized, assessor-blind, pilot trial. It is designed in accordance with the Standards for Reporting Interventions in Controlled Trials of Acupuncture. A total of 44 MND participants who meet the inclusion and exclusion criteria will be enrolled, and each will be randomly assigned to 1 of 2 groups of 22 subjects. Each subject will visit 24 times over 12 weeks and receive either acupuncture or NF-acupuncture combined treatment. At visit 25 (week 13), a follow-up evaluation will be performed, and then the investigator will analyze the results. The primary outcome is defined by the Korean version of the Montreal Cognitive Assessment score from screening to visit 25. The secondary outcome includes the following: change in Alzheimer Disease Assessment Scale-Cognitive, the Korean version of the Beck Depression Inventory, Body Awareness Questionnaire, delayed matching to sample task scores, and functional near-infrared spectroscopy values, from visit 1 to visit 25; heart rate variability values from visit 1 to visit 5, visit 9, visit 13, visit 21, visit 25; breath per minute values from visit 1 to visit 1 to 25.

Discussion: We will evaluate the effectiveness and safety of combined NF-acupuncture therapy, and expect that it will serve as the basis for the use of NF together with acupuncture in the clinical setting.

Trial Registration Number: KCT0004972 (registered in Clinical Research Information Service of the Republic of Korea, https://cris.nih.go.kr/cris/search/detailSearch.do/16239).
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http://dx.doi.org/10.1097/MD.0000000000027218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448021PMC
September 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

Electrostatic Stabilization of Nano Liquid Metals in Doped Nonpolar Liquids.

Small 2021 Nov 8;17(45):e2104143. Epub 2021 Oct 8.

Department of Chemical Engineering, Myongji University, 116 Myongji-ro, Cheoin-gu, Yongin, Gyeonggi-do, 17058, Korea.

Liquid metals and alloys are attracting renewed attention owing to their potential for application in various advanced technologies. Eutectic gallium-indium (EGaIn) has been focused on in particular because of its integrated advantages of high conductivity, low melting point, and low toxicity. In this study, the colloidal behavior of nano-dispersed EGaIn in nonpolar oils is investigated. Although the nonpolar oil continuous phase is commonly considered to be free of electric charges, electrostatic repulsion appears to be crucial in the colloidal stabilization of the nano-dispersed EGaIn phases, the modulation of which is possible by doping the oil phases with different types of oil-soluble surfactants. The qualitative correlation between the observed colloidal stabilities and the "zero field" particle mobilities inferred from the field-dependent electrophoretic mobilities indicates that the electric charging of EGaIn particles in surfactant-doped nonpolar oils is a static phenomenon that is maintained in equilibrium, rather than a solely field-induced process. A systematic investigation of the charging properties of these unique biphasic particles, consisting of the liquid Ga-In bulk and the solid Ga O surface that formed spontaneously, reveals the complicated system-dependent nature of the charging mechanisms mediated by ionic and nonionic surfactants in nonpolar media.
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http://dx.doi.org/10.1002/smll.202104143DOI Listing
November 2021

An Intestine-Derived Hdl As A Novel Regulator of the Activity of Gut-Derived LPS: Ushering In A New Era of Research On the Gut-Liver Axis.

Gastroenterology 2021 Sep 24. Epub 2021 Sep 24.

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.

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http://dx.doi.org/10.1053/j.gastro.2021.09.045DOI Listing
September 2021

Risk Factors Preventing Immediate Fall Detection: A Study Using Zero-Inflated Negative Binomial Regression.

Asian Nurs Res (Korean Soc Nurs Sci) 2021 Oct 17;15(4):272-277. Epub 2021 Sep 17.

Red Cross College of Nursing, Chung-Ang University, Seoul, Republic of Korea. Electronic address:

Purpose: Falls are the most common accidents in healthcare facilities, and timely intervention can have a positive effect on the hazards and trauma experienced by patients after a fall. This study determined the factors affecting the time taken to detect a fall.

Methods: A total of 3,470 cases of falls reported through the Korea Patient Safety Reporting and Learning System were included in the analysis. A zero-inflated negative binomial regression method was used for this retrospective secondary data analysis study.

Results: There were 537 patients whose falls were not detected immediately; the count model was used to predict risk factors that delayed fall detection. Women aged 60-69 years-compared to those below 60 years and an evening nursing shift, compared to a day shift-were identified as significant factors. The fall detection time of about 2,933 patients was zero; therefore, the logit model was applied to predict a patient's possibility of belonging to the group whose fall was detected immediately. Comparisons of tertiary hospitals with general hospitals and hospitals, of the evening shift with the day shift, and of the day shift with the night shift indicated significant influencing factors.

Conclusions: These findings can assist nurses in recognizing patient and hospital characteristics related to delayed fall detection. Strategies to improve patient safety in healthcare facilities that focus on patient characteristics such as age can be recommended. Furthermore, nurse staffing requires improvement to detect fall incidents immediately.
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http://dx.doi.org/10.1016/j.anr.2021.09.001DOI Listing
October 2021

Physical and Mental Health Factors Associated with Poor Nutrition in Elderly Cancer Survivors: Insights from a Nationwide Survey.

Int J Environ Res Public Health 2021 09 3;18(17). Epub 2021 Sep 3.

Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, 38 Bangdong-gil, Sacheon-myeon, Gangneung-si 25440, Korea.

Elderly cancer survivors (patients with any stage of cancer or a history of cancer) are precious members of our society and they can be easily found in various types of surveys. As is well known, good nutrition is important in elderly people suffering from cancer. Proper nutritional evaluation and intervention not only improves their quality of life but also helps them to receive adequate treatment, thereby prolonging individual survival and reducing social healthcare costs. In this study, we retrieved elderly cancer survivors from national survey data and assessed their nutritional status as good or bad. Then, we described the individual, physical, and mental health factors between people with good and bad nutrition. Physical and psychological variables associated with poor nutritional status were evaluated through regression analysis. We investigated data from the 2017 National Survey of Older Persons, and cancer patients aged 65 years or over were eligible. A total of 360 adults were enrolled and more than half (57.2%, = 206) were in a poor nutritional status. We applied individual variable-adjusted statistical models and discovered that limited instrumental activities of daily living (IADL) (OR 2.15, 95% CI 1.08-4.28) and poor subjective health status (OR 1.74, 95% CI 1.00-3.02) were significantly associated with poor nutrition on logistic regression. Our research findings suggested that IADL and self-rated health status needed to be addressed in old cancer survivors at nutritional risk. The early recognition and management of nutrition in these populations might help them to live longer and have a better quality of life, eventually reducing socioeconomic burdens.
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http://dx.doi.org/10.3390/ijerph18179313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431383PMC
September 2021

Crossing the Rubicon: Adipose Tissue Autophagy Breaks Out NAFLD.

Cell Mol Gastroenterol Hepatol 2021 27;12(5):1877-1878. Epub 2021 Aug 27.

Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

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http://dx.doi.org/10.1016/j.jcmgh.2021.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591194PMC
August 2021

Human Blood Vessel Organoids Penetrate Human Cerebral Organoids and Form a Vessel-Like System.

Cells 2021 08 9;10(8). Epub 2021 Aug 9.

Futuristic Animal Resource and Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang 28116, Korea.

Vascularization of tissues, organoids and organ-on-chip models has been attempted using endothelial cells. However, the cultured endothelial cells lack the capacity to interact with other somatic cell types, which is distinct from developing vascular cells in vivo. Recently, it was demonstrated that blood vessel organoids (BVOs) recreate the structure and functions of developing human blood vessels. However, the tissue-specific adaptability of BVOs had not been assessed in somatic tissues. Herein, we investigated whether BVOs infiltrate human cerebral organoids and form a blood-brain barrier. As a result, vascular cells arising from BVOs penetrated the cerebral organoids and developed a vessel-like architecture composed of CD31 endothelial tubes coated with SMA or PDGFR mural cells. Molecular markers of the blood-brain barrier were detected in the vascularized cerebral organoids. We revealed that BVOs can form neural-specific blood-vessel networks that can be maintained for over 50 days.
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http://dx.doi.org/10.3390/cells10082036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393185PMC
August 2021

Comparison of RT-PCR, RT-nested PCRs, and real-time PCR for diagnosis of severe fever with thrombocytopenia syndrome: a prospective study.

Sci Rep 2021 08 18;11(1):16764. Epub 2021 Aug 18.

Department of Internal Medicine, School of Medicine, Pusan National University, Pusan, Republic of Korea.

We designed a highly sensitive reverse transcription nested polymerase chain reaction targeting the M-segment (NPCR-M) of severe fever with thrombocytopenia syndrome (SFTS) virus. NPCR-M was performed in parallel with three other referenced PCR assays QPCR-S, PCR-M, and NPCR-S to assess their clinical usefulness as routine diagnostic techniques for SFTS. In this multi-centered prospective study, 122 blood samples from 38 laboratory-confirmed SFTS patients and 85 control samples were used. The results demonstrated that QPCR-S and NPCR-S had better sensitivity rate up to 21 days after symptom onset however, the PCR-M showed poor sensitivity after 7 days of symptom onset. Our designed NPCR-M had a higher detection rate up to 40 days from symptom onset and revealed the persistence of SFTSV RNA in the early convalescent phase. No false-positive results were seen for the control samples. Additionally, NPCR-M showed positive results for a sample that initially showed negative results from other PCRs and for many other samples collected in the convalescent phase of SFTS. Our designed nested PCR is suitable for SFTSV detection in patients' blood collected in the acute and early convalescent phase of SFTS, and shows better sensitivity and high specificity even up to 40 days after symptom onset.
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http://dx.doi.org/10.1038/s41598-021-96066-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373928PMC
August 2021

Approach to Bethesda system category III thyroid nodules according to US-risk stratification.

Endocr J 2021 Aug 18. Epub 2021 Aug 18.

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

This study evaluated how to manage Bethesda category III (Bethesda III) (atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS]) thyroid nodules according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) to reduce unnecessary surgeries. A total of 161 thyroid nodules diagnosed as Bethesda III underwent surgery from 2016 to 2019. Ultrasonography-guided fine-needle aspiration (US-FNA) or core needle biopsy (CNB) was used for repeat examination. K-TIRADS category was assigned to the thyroid nodules. The proportion of malignancy in Bethesda III nodules confirmed by surgery were significantly increased in proportion relative to K-TIRADS with 60.0% low suspicion, 88.2% intermediate suspicion, and 100% high suspicion nodules (p < 0.001). The proportion of malignancy in AUS and FLUS were significantly different (94.2% vs. 40.0% p = 0.003). The proportion of malignancy in AUS increased with K-TIRADS categories, but there was no difference in FLUS. All K-TIRADS high suspicion nodules were AUS as papillary carcinomas (99%), while 80% of FLUS nodules and 50% of follicular carcinomas showed K-TIRADS low suspicion. In 116 nodules with repeat FNA or CNB after initial Bethesda III results, the conclusive result rate was significantly increased in proportion to K-TIRADS with 58.3% low suspicion, 83.3% intermediate suspicion, and 88.8% high suspicion nodules (p = 0.015). K-TIRADS low suspicion nodules of Bethesda III nodules should be managed after risk-benefit consideration rather than immediate surgery or repeat examination. K-TIRADS for Bethesda III nodules can predict papillary carcinoma well, but not follicular carcinoma.
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http://dx.doi.org/10.1507/endocrj.EJ21-0300DOI Listing
August 2021

The beneficial effects of menopausal hormone therapy on renal survival in postmenopausal Korean women from a nationwide health survey.

Sci Rep 2021 07 29;11(1):15418. Epub 2021 Jul 29.

Department of Statistics and Actuarial Science, Soongsil University, 369 Sangdo-ro, Dongjak-gu, Seoul, 06978, Republic of Korea.

Several studies have demonstrated the nephroprotective effects of estrogen on renal damage. In light of the inconsistent results of previous findings, this study aims to evaluate the in-depth role of menopausal hormone therapy (MHT) on the development of end stage renal disease (ESRD). 3,109,506 Korean adult women who had undergone a medical examination in 2009 (index year) were initially identified for inclusion in this study. We excluded subjects had not experienced menopause naturally, had data missing for at least one variable, and were diagnosed with ESRD within 1 year from the index year. MHT data was obtained from self-reporting questionnaires and the primary outcome was the development of ESRD from the index year until December 31, 2018. A final total of 1,460,311 subjects were included in this study. The participants were divided into four groups according to the duration of MHT; no history of MHT, MHT < 2 years, 2 ≤ MHT < 5 years, MHT ≥ 5 years. During the 9-year study period, a total of 4905 participants developed ESRD. The participants who had a history of MHT use were found to have a 30% reduced risk of developing ESRD. Results from the subgroup analyses were similar to that of the primary study. The findings in this study demonstrate the beneficial effects of MHT on the development of ESRD in postmenopausal women. Based on results, our study may offer suggestions for further studies to investigate the therapeutic options on kidney disease.
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http://dx.doi.org/10.1038/s41598-021-93847-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322273PMC
July 2021

SARS-CoV-2 Restructures the Host Chromatin Architecture.

bioRxiv 2021 Jul 21. Epub 2021 Jul 21.

SARS-CoV-2 has made >190-million infections worldwide, thus it is pivotal to understand the viral impacts on host cells. Many viruses can significantly alter host chromatin , but such roles of SARS-CoV-2 are largely unknown. Here, we characterized the three-dimensional (3D) genome architecture and epigenome landscapes in human cells after SARS-CoV-2 infection, revealing remarkable restructuring of host chromatin architecture. High-resolution Hi-C 3.0 uncovered widespread A compartmental weakening and A-B mixing, together with a global reduction of intra-TAD chromatin contacts. The cohesin complex, a central organizer of the 3D genome, was significantly depleted from intra-TAD regions, supporting that SARS-CoV-2 disrupts cohesin loop extrusion. Calibrated ChIP-Seq verified chromatin restructuring by SARS-CoV-2 that is particularly manifested by a pervasive reduction of euchromatin modifications. Built on the rewired 3D genome/epigenome maps, a modified activity-by-contact model highlights the transcriptional weakening of antiviral interferon response genes or virus sensors (e.g., ) incurred by SARS-CoV-2. In contrast, pro-inflammatory genes (e.g. ) high in severe infections were uniquely regulated by augmented H3K4me3 at their promoters. These findings illustrate how SARS-CoV-2 rewires host chromatin architecture to confer immunological gene deregulation, laying a foundation to characterize the long-term epigenomic impacts of this virus.
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http://dx.doi.org/10.1101/2021.07.20.453146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312896PMC
July 2021

A Deep Dive: SIWV Tetra-Peptide Enhancing the Penetration of Nanotherapeutics into the Glioblastoma.

ACS Biomater Sci Eng 2021 Jul 1. Epub 2021 Jul 1.

Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

Glioblastoma multiforme (GBM) is the most aggressive malignant tumor. It is difficult to regulate GBM using conventional chemotherapy-based methods due to its anatomical structure specificity, low drug targeting ability, and limited penetration depth capability to reach the tumor interior. Numerous approaches have been proposed to overcome such issues, including nanoparticle-based drug delivery system (DDS) with the development of GBM site targeting and penetration depth enhancing moieties (e.g., peptides, sugars, proteins, etc.). In this study, we prepared four different types of nanoparticles, which are based on porous silicon nanoparticles (pSiNPs) incorporating polyethylene glycol (PEG), iRGD peptide (well-known cancer targeting peptide), and SIWV tetra-peptide (a recently disclosed GBM-targeting peptide), and analyzed their deep-tumor penetration abilities in cell spheroids, in GBM patient-derived tumoroids, and in GBM xenograft mice. We found that SIWV tetra-peptide significantly enhanced the penetration depth of pSiNPs, and its therapeutic formulation (temozolomide-loaded/SIWV-functionalized pSiNPs) showed a higher anticancer efficacy compared with other formulations. These findings hold great promise for the development of nanotherapeutics and peptide-conjugated drugs for GBM.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00653DOI Listing
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

Effects of zoledronic acid on osteonecrosis and acute lymphoblastic leukemia treatment efficacy in preclinical models.

Pediatr Blood Cancer 2021 Oct 14;68(10):e29183. Epub 2021 Jun 14.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Background: Osteonecrosis is a devastating side effect of acute lymphoblastic leukemia (ALL) therapy. Associations between bone density loss and osteonecrosis have sparked interest in using bisphosphonates to reduce this complication.

Procedure: We assessed the impact of zoledronic acid (ZA) on the development of osteonecrosis in murine models when used either throughout therapy (continuous administration) or late in therapy after vascular lesions have developed but before osteonecrosis has occurred. Effects on bone density were measured using microcomputed tomography (μCT)-assessed tibial cortical thickness, while osteonecrosis was assessed histologically in the distal femur. Effects on antileukemic efficacy of chemotherapy were evaluated in both immunocompetent/syngeneic and patient-derived xenograft (PDX) models.

Results: Continuous administration of ZA with chemotherapy prevented chemotherapy-associated bone loss (p < .001) and reduced osteonecrosis (p = .048). Late initiation of ZA diminished bone loss (p < .001) but had no impact on the development of osteonecrosis (p = .93). In the immunocompetent murine ALL model, mice treated with ZA and chemotherapy succumbed to leukemia sooner than mice treated with chemotherapy alone (p = .046). Analysis using PDX showed a nonsignificant decrease in survival with ZA (p = .17).

Conclusion: Our data indicate ZA may prevent osteonecrosis if begun with chemotherapy but showed no benefit when administered later in therapy. However, ZA may also reduce the antileukemic efficacy of chemotherapy.
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http://dx.doi.org/10.1002/pbc.29183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384719PMC
October 2021

Relationship between Low Vegetable Consumption, Increased High-Sensitive C-Reactive Protein Level, and Cardiometabolic Risk in Korean Adults with Tae-Eumin: A Cross-Sectional Study.

Evid Based Complement Alternat Med 2021 11;2021:3631445. Epub 2021 May 11.

Future Medicine Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.

An anti-inflammatory diet has many beneficial effects on cardiometabolic diseases. Constitution type of traditional Korean medicine can predict cardiometabolic risk factors. We examined the relationship between vegetable consumption and the high-sensitive C-reactive protein (hs-CRP) level on cardiometabolic risk factors in Korean adults by constitution types. Data from 1,983 eligible participants (mean age, 44.3 years) were included in the present cross-sectional study. The inflammatory status of the participants was categorized into low- (<3.0 mg/L) or high-risk (≥3.0 mg/L) groups based on their constitution types. Cardiometabolic risk factors (abdominal obesity, elevated triglycerides, reduced high-density lipoprotein-cholesterol, elevated blood pressure, elevated fasting plasma glucose, and ≥2 concurrent cardiovascular diseases (CVDs) risk factors) and dietary assessment of the participants were assessed. A total of 11.1% of Tae-eumin (TE) and 4.9% of non-TE groups had a higher hs-CRP level (TE: 6.6 ± 0.2, non-TE: 8.4 ± 0.3) than a low hs-CRP level TE and non-TE (TE: 0.9 ± 0.1, non-TE: 0.6 ± 0.1). Vegetable consumption of <91.5 g/day was highly associated with a high-risk hs-CRP level (adjusted odds ratio (ORs): second tertile (T2): 2.290, (95% confidence interval (CI): 1.285-4.082); first tertile (T1): 2.474 (95% CI: 1.368-4.475), =0.003) compared with that of the highest (T3) in TE. Low (T1 and T2) vegetable consumption was associated with a 54-63% increased prevalence of more than two concurrent CVDs risk factors compared with that of the highest in the TE group (=0.012). Higher vegetable consumption greatly decreased the prevalence of CVDs risk factors by 63-86% in the low-risk and high-risk hs-CRP TE groups. Our results highlight the cardioprotective effects of higher consumption of vegetables in Korean adults with TE. Evidence-based clinical risk factor management and multifaceted approaches at the community and population levels targeting prevention in high-burden groups are recommended to reduce the premature mortality attributed to CVD.
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http://dx.doi.org/10.1155/2021/3631445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131133PMC
May 2021

Low nutritional status links to the prevalence of pre-metabolic syndrome and its cluster in metabolically high-risk Korean adults: A cross-sectional study.

Medicine (Baltimore) 2021 May;100(20):e25905

Future Medicine Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, Republic of Korea.

Abstract: Diet plays a crucial role as a modifiable risk factor related to the development of metabolic syndrome (MetS) and its cluster. Constitution type of traditional Korean medicine has shown accuracy to predict the risk for MetS. We attempted to examine the association between nutritional status, pre-MetS, and its cluster in Korean adults by their constitution type.Participants aged 30 to 55 years who had no cancer or cardiovascular diseases (CVDs) were assigned to join in the present study. Pre-MetS was defined as ≥2 of the following factors: abdominal obesity; elevated triglycerides (TG); reduced high-density lipoprotein cholesterol (HDL-C); elevated blood pressure (BP); and elevated fasting plasma glucose (FPG). Constitution type was categorized into Tae-Eumin (TE) or non-TE. Dietary assessment of the subjects were surveyed using a short-form of the food frequency questionnaire (FFQ) and the nutrition quotient (NQ), which uses 4 factors, namely, balance, diversity, moderation, and dietary behavior.A total of 986 subjects were evaluated by constitution type with MetS status. Of these subjects, 48.6% had pre-MetS, 89.5% were obese and had the highest waist circumference (WC) in Pre-MetS TE. BP, FPG, TG were higher, while HDL-C was lower, than normal TE or non-TE both in Pre-MetS TE and non-TE. The prevalence of pre-MetS was positively associated with lower status of dietary behavior (odds ratio [ORs]: 2.153, 95% confidence interval [CI]: 1.179-3.931) while negatively related to higher vegetables and fruits intakes (ORs: 0.594, 95% CI: 0.359-0.983) in TE. Lower status of NQ had about 2 times higher risk of Pre-MetS (ORs: 1.855, 95% CI: 1.018-3.380) and abdominal obesity (ORs: 2.035, 95% CI: 1.097-3.775) in TE compared with higher status of NQ after controlling for covariates.Poor diet was a key contributor to the development of Pre-MetS and abdominal obesity in Korean adults with TE. Customized nutrition care and integrated medicinal approaches are strongly suggested to conduct optimal preventive care for people who are vulnerable to health risk.
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http://dx.doi.org/10.1097/MD.0000000000025905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137084PMC
May 2021

Two Helminthic Cases of Human Mummy Remains from Joseon-Period Graves in Korea.

Korean J Parasitol 2021 Apr 22;59(2):149-152. Epub 2021 Apr 22.

Department of Parasitology, Dankook University College of Medicine, Cheonan 31116, Korea.

Our previous research on coprolite specimens from the mummies of Joseon Dynasty (1392-1910 CE) has revealed various species of parasite eggs. Herein, we added 2 new helminthic cases of human remains from Joseon-period graves in the Republic of Korea (Korea). The organic materials precipitated on the hip bones of 2 half-mummied cases (Goryeong and Gwangmyeong cases) were collected, rehydrated, and examined by a microscope. In the sample from Goryeong-gun (gun=County), ova of Trichuris trichiura, Clonorchis sinensis, and Metagonimus spp. were detected, and eggs of T. trichiura and A. lumbricoides were found from the sample of Gwangmyeong-si (si=City). By adding this outcome to the existing data pool, we confirm our previous estimates of Joseon-period parasite infection rates. The overall rates of A. lumbricoides, T. trichiura, and C. sinensis decreased dramatically from Joseon to the modern period. In Goryeong mummy specimen, we also found Metagonimus spp. eggs that has rarely been detected in archaeological samples so far.
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http://dx.doi.org/10.3347/kjp.2021.59.2.149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106984PMC
April 2021

Deep Residual Networks for User Authentication via Hand-Object Manipulations.

Sensors (Basel) 2021 Apr 23;21(9). Epub 2021 Apr 23.

ImagineX Lab, Graduate School of Technology and Innovation Management, Hanyang University, Seoul 04763, Korea.

With the ubiquity of wearable devices, various behavioural biometrics have been exploited for continuous user authentication during daily activities. However, biometric authentication using complex hand behaviours have not been sufficiently investigated. This paper presents an implicit and continuous user authentication model based on hand-object manipulation behaviour, using a finger-and hand-mounted inertial measurement unit (IMU)-based system and state-of-the-art deep learning models. We employed three convolutional neural network (CNN)-based deep residual networks (ResNets) with multiple depths (i.e., 50, 101, and 152 layers) and two recurrent neural network (RNN)-based long short-term memory (LSTMs): simple and bidirectional. To increase ecological validity, data collection of hand-object manipulation behaviours was based on three different age groups and simple and complex daily object manipulation scenarios. As a result, both the ResNets and LSTMs models acceptably identified users' hand behaviour patterns, with the best average accuracy of 96.31% and F1-score of 88.08%. Specifically, in the simple hand behaviour authentication scenarios, more layers in residual networks tended to show better performance without showing conventional degradation problems (the ResNet-152 > ResNet-101 > ResNet-50). In a complex hand behaviour scenario, the ResNet models outperformed user authentication compared to the LSTMs. The 152-layered ResNet and bidirectional LSTM showed an average false rejection rate of 8.34% and 16.67% and an equal error rate of 1.62% and 9.95%, respectively.
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http://dx.doi.org/10.3390/s21092981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122988PMC
April 2021

CycleMorph: Cycle consistent unsupervised deformable image registration.

Med Image Anal 2021 07 12;71:102036. Epub 2021 Mar 12.

Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Electronic address:

Image registration is a fundamental task in medical image analysis. Recently, many deep learning based image registration methods have been extensively investigated due to their comparable performance with the state-of-the-art classical approaches despite the ultra-fast computational time. However, the existing deep learning methods still have limitations in the preservation of original topology during the deformation with registration vector fields. To address this issues, here we present a cycle-consistent deformable image registration, dubbed CycleMorph. The cycle consistency enhances image registration performance by providing an implicit regularization to preserve topology during the deformation. The proposed method is so flexible that it can be applied for both 2D and 3D registration problems for various applications, and can be easily extended to multi-scale implementation to deal with the memory issues in large volume registration. Experimental results on various datasets from medical and non-medical applications demonstrate that the proposed method provides effective and accurate registration on diverse image pairs within a few seconds. Qualitative and quantitative evaluations on deformation fields also verify the effectiveness of the cycle consistency of the proposed method.
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http://dx.doi.org/10.1016/j.media.2021.102036DOI Listing
July 2021

Expanding the Non-Invasive Diagnosis of Acute Rejection in Kidney Transplants Through Detection of Donor-Derived DNA in Urine: Proof-of-Concept Study.

Ann Lab Med 2021 Sep;41(5):469-478

Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background: Approximately 10%-20% of kidney transplant (KT) recipients suffer from acute rejection (AR); thus, sensitive and accurate monitoring of allograft status is recommended. We evaluated the clinical utility of donor-derived DNA (dd-DNA) detection in the urine of KT recipients as a non-invasive means for diagnosing AR.

Methods: Urine samples serially collected from 39 KT recipients were tested for 39 single-nucleotide variant loci selected according to technical criteria (i.e., high minor allele frequency and low analytical error) using next-generation sequencing. The fraction of dd-DNA was calculated and normalized by the urine creatinine (UCr) level (%dd-DNA/UCr). The diagnostic performance of %dd-DNA/UCr for AR was assessed by ROC curve analysis.

Results: There was an increasing trend of %dd-DNA/UCr in the AR group before subsequent graft injury, which occurred before (median of 52 days) histological rejection. The serum creatinine (SCr) level differed significantly between the AR and non-AR groups at two and four months of follow-up, whereas %dd-DNA/UCr differed between the groups at six months of follow-up. The combination of %dd-DNA/UCr, SCr, and spot urine protein (UPtn)/UCr showed high discriminating power, with an area under the ROC curve of 0.93 (95% confidence interval: 0.81-1.00) and a high negative predictive value of 100.0%.

Conclusions: Although the dd-DNA-based test cannot eliminate the need for biopsy, the high negative predictive value of this marker could increase the prebiopsy probability of detecting treatable injury to make biopsy an even more effective diagnostic tool.
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http://dx.doi.org/10.3343/alm.2021.41.5.469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041594PMC
September 2021

Role of obesity-induced inflammation in the development of insulin resistance and type 2 diabetes: history of the research and remaining questions.

Ann Pediatr Endocrinol Metab 2021 Mar 31;26(1):1-13. Epub 2021 Mar 31.

Soonchunhyang Institute of MediBio Science (SIMS), Department of Integrated Biomedical Science, Soonchunhyang University, Cheonan, Korea.

The prevalence of obesity has increased alarmingly both worldwide and in Korea. This has also dramatically increased the prevalence of chronic obesity-associated diseases, including type 2 diabetes (T2D). Extensive studies on the molecular etiology of T2D have revealed several potential mechanisms by which obesity induces the development of insulin resistance and T2D. One of these is low-grade chronic inflammation. Studies hinting at the existence of this phenomenon were first published about 30 years ago. Ten years later, several seminal papers confirmed its existence, which then led to a rapid and massive escalation of research in this field. Today, the notion that obesity-induced inflammation mediates T2D is now well-accepted. This paper will review the key developments in this field, including the discovery that obesity-induced inflammation and insulin resistance is mainly regulated by adipose tissue-resident immune cells, particularly those in visceral adipose tissue. This review further details the research areas, including (1) the obesity-related factors that induce adipose tissue macrophage (ATM) inflammation, (2) the precise effector functions by which adipose tissue immune cells promote insulin resistance, (3) whether there are early immunological events that have an outsize effect on later events and could be targeted to arrest the development of insulin resistance, (4) the roles played by nonimmunological functions of ATMs and other immune cells, and (5) whether there are noncanonical immune responses to obesity (i.e., immune responses that are unique to obesity and cannot be detected by following the discoveries in the classical immunity field).
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http://dx.doi.org/10.6065/apem.2040188.094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026341PMC
March 2021

Crystal structure of human interleukin-2 in complex with TCB2, a new antibody-drug candidate with antitumor activity.

Oncoimmunology 2021 03 16;10(1):1899671. Epub 2021 Mar 16.

Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, Republic of Korea.

Immunotherapy via interleukin-2 (IL-2) mediated activation of anti-tumor immune response is a promising approach for cancer treatment. The multi-potent cytokine, IL-2 has a central role in immune cell activation and homeostasis. Since IL-2 preferentially activates immunosuppressive T regulatory cells by IL-2Rα dependent manner, blocking IL-2:IL-2Rα interaction is a key to amplify the IL-2 activity in effector T cells toward anti-tumor response. Anti-IL-2 monoclonal antibodies are good candidates to control the IL-2:IL-2Rα interaction. In a previous study, we developed a new IL-2Rα mimetic antibody, TCB2, and showed that the human IL-2(hIL-2):TCB2 complex can stimulate T effector cells specifically and elicit potent anti-cancer immunotherapeutic effect, especially when administered in combination with immune checkpoint inhibitors. To understand the molecular mechanism, we determined the crystal structure of TCB2-Fab in a complex with hIL-2 at 2.5 Å resolution. Our structural analysis reveals that TCB2 binds to the central area of the hIL-2Rα binding region on hIL-2, and binding angle and epitope are different from previously known hIL-2Rα mimicking antibody NARA1 which recognizes the top part of hIL-2. TCB2 binding to hIL-2 also induces an allosteric effect that increases the affinity for the hetero-dimeric hIL-2 receptor, IL-2R(β + γ), on effector T cells.
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http://dx.doi.org/10.1080/2162402X.2021.1899671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971329PMC
March 2021

Dietary glutamic acid and aspartic acid as biomarkers for predicting diabetic retinopathy.

Sci Rep 2021 03 31;11(1):7244. Epub 2021 Mar 31.

Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.

The screening rate of diabetic retinopathy (DR) is low despite the importance of early diagnosis. We investigated the predictive value of dietary glutamic acid and aspartic acid for diagnosis of DR using the Korea National Diabetes Program cohort study. The 2067 patients with type 2 diabetes without DR were included. The baseline intakes of energy, glutamic acid and aspartic acid were assessed using a 3-day food records. The risk of DR incidence based on intake of glutamic acid and aspartic acid was analyzed. The DR group was older, and had higher HbA1c, longer DM duration, lower education level and income than non-DR group (all p < 0.05). The intake of total energy, glutamic acid and aspartic acid were lower in DR group than non-DR group (p = 0.010, p = 0.025 and p = 0.042, respectively). There was no difference in the risk of developing DR according to the intake of glutamic acid and ascorbic acid. But, aspartic acid intake had a negative correlation with PDR. Hence, the intake of glutamic acid and aspartic acid did not affect in DR incidence. However, lower aspartic acid intake affected the PDR incidence.
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http://dx.doi.org/10.1038/s41598-021-83165-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012375PMC
March 2021

Emerging pathogenic role of peripheral blood factors following BBB disruption in neurodegenerative disease.

Ageing Res Rev 2021 07 24;68:101333. Epub 2021 Mar 24.

Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu, 41062, Republic of Korea. Electronic address:

The responses of central nervous system (CNS) cells such as neurons and glia in neurodegenerative diseases (NDs) suggest that regulation of neuronal and glial functions could be a strategy for ND prevention and/or treatment. However, attempts to develop such therapeutics for NDs have been hindered by the challenge of blood-brain barrier (BBB) permeability and continued constitutive neuronal loss. These limitations indicate the need for additional perspectives for the prevention/treatment of NDs. In particular, the disruption of the blood-brain barrier (BBB) that accompanies NDs allows brain infiltration by peripheral factors, which may stimulate innate immune responses involved in the progression of neurodegeneration. The accumulation of blood factors like thrombin, fibrinogen, c-reactive protein (CRP) and complement components in the brain has been observed in NDs and may activate the innate immune system in the CNS. Thus, strengthening the integrity of the BBB may enhance its protective role to attenuate ND progression and functional loss. In this review, we describe the innate immune system in the CNS and the contribution of blood factors to the role of the CNS immune system in neurodegeneration and neuroprotection.
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http://dx.doi.org/10.1016/j.arr.2021.101333DOI Listing
July 2021

Modulation of SETDB1 activity by APQ ameliorates heterochromatin condensation, motor function, and neuropathology in a Huntington's disease mouse model.

J Enzyme Inhib Med Chem 2021 Dec;36(1):856-868

Department of Chemical & Molecular Engineering/Applied Chemistry, Center for Bionano Intelligence Education and Research, Hanyang University, Ansan, Republic of Korea.

The present study describes evaluation of epigenetic regulation by a small molecule as the therapeutic potential for treatment of Huntington's disease (HD). We identified 5-allyloxy-2-(pyrrolidin-1-yl)quinoline (APQ) as a novel SETDB1/ESET inhibitor using a combined and cell based screening system. APQ reduced SETDB1 activity and H3K9me3 levels in a HD cell line model. In particular, not only APQ reduced H3K9me3 levels in the striatum but it also improved motor function and neuropathological symptoms such as neuronal size and activity in HD transgenic (YAC128) mice with minimal toxicity. Using H3K9me3-ChIP and genome-wide sequencing, we also confirmed that APQ modulates H3K9me3-landscaped epigenomes in YAC128 mice. These data provide that APQ, a novel small molecule SETDB1 inhibitor, coordinates H3K9me-dependent heterochromatin remodelling and can be an epigenetic drug for treating HD, leading with hope in clinical trials of HD.
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http://dx.doi.org/10.1080/14756366.2021.1900160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008885PMC
December 2021
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