Publications by authors named "Ju-Hyun Lee"

150 Publications

Effect of a hospital-wide campaign on COVID-19 vaccination uptake among healthcare workers in the context of raised concerns for life-threatening side effects.

PLoS One 2021 1;16(10):e0258236. Epub 2021 Oct 1.

Division of Infectious Disease, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si, Gyeonggi-do, Republic of Korea.

Background: All healthcare workers (HCWs) in Yongin Severance Hospital were allocated to receive the ChAdOx1 nCov-19 vaccine according to national policy. A report of thrombosis and thrombocytopenia syndrome (TTS) associated with ChAdOx1 nCoV-19 led to hesitancy about receiving the second dose among HCWs who had received the first dose.

Methods: From 7 to 14 May, 2021, we performed a survey to identify the factors associated with hesitancy about receiving the second vaccine dose among HCWs at the hospital who had received the first dose of the vaccine. Based on survey results, a hospital-wide campaign was implemented on 18 May 2021 to improve vaccine coverage. HCWs who completed the second dose completed a self-administered questionnaire to evaluate the effect of the campaign.

Findings: Of 1,171 HCWs who had received the first dose of the vaccine, 71.5% completed the online survey, of whom 3.7% refused to take the second dose and 22.3% showed hesitancy. Hesitancy to receive a second dose was significantly associated with age under 30 years and concerns about TTS, and was less common among those who trusted effectiveness and safety of the vaccine. Among HCWs who received the first dose, 96.2% completed vaccination with the second dose between 27 May and 4 June, 2021. Of those who answered the questionnaire asked about the timing of their decision to receive the second dose, 57.1% reported that they were motivated by the hospital-wide campaign.

Conclusion: A tailored intervention strategy based on a survey can improve COVID-19 vaccination uptake among HCWs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258236PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486118PMC
October 2021

Evaluation of the need for cytoreduction and its potential carcinogenicity in children and young adults with myeloproliferative neoplasms.

Ann Hematol 2021 Oct 30;100(10):2567-2574. Epub 2021 Jul 30.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, 13620, Gyeonggi-do, Republic of Korea.

Myeloproliferative neoplasms are rare at a young age, and few reports have described the disease characteristics and outcomes in this group. This study aimed to elucidate the clinical course of essential thrombocythemia (ET) and polycythemia vera (PV) in children and young adults aged <39 years focusing on thromboembolic events (TE) and second primary malignancies (SPMs). A total of 990 patients who were diagnosed from 2008 to 2017 were included by analyzing the Health Insurance Review and Assessment Service database in Korea. The incidence was 2.53 per 1,000,000 for ET (643 patients; 276 male patients; median 31 years) and 1.37 per 1,000,000 for PV (347 patients; 309 male patients; median 32 years). Three ET patients developed secondary acute myelogenous leukemia and three developed secondary myelofibrosis. The 5-year cumulative incidence of TE was 14.2% in ET and 21.3% in PV. Thus, the incidence was higher in PV; in particular, arterial TE (ATE) was evidently higher in PV than in ET. The 5-year cumulative incidence of SPMs was 2.5% in ET and 2.6% in PV. While the use of both aspirin and hydroxyurea reduced the incidence of ATE, hydroxyurea significantly increased the incidence of SPMs. The incidence of ET and PV was very low, and ET was more common than PV in children and young adults. The high incidence of TE in young patients suggests the importance of thrombosis prevention. However, hydroxyurea appears to increase the incidence of SPMs; therefore, the risks and benefits should be considered.
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http://dx.doi.org/10.1007/s00277-021-04527-7DOI Listing
October 2021

A randomised phase II study of oxaliplatin/5-FU (mFOLFOX) versus irinotecan/5-FU (mFOLFIRI) chemotherapy in locally advanced or metastatic biliary tract cancer refractory to first-line gemcitabine/cisplatin chemotherapy.

Eur J Cancer 2021 Sep 22;154:288-295. Epub 2021 Jul 22.

Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam, 13620, Republic of Korea. Electronic address:

Background: In locally advanced or metastatic biliary tract cancer (BTC), second-line chemotherapy is challenging after progression from first-line gemcitabine/cisplatin. This study evaluated whether irinotecan/5-fluorouracil (5-FU; mFOLFIRI) was superior to oxaliplatin/5-FU (mFOLFOX) as a second-line treatment in BTC.

Patients And Methods: Patients diagnosed with BTC with disease progression after prior gemcitabine/cisplatin were randomised (1:1) to either mFOLFOX (control arm) or mFOLFIRI (experimental arm). Randomisation was stratified by tumour location (intrahepatic versus extrahepatic versus gallbladder versus ampulla of Vater) and ECOG performance status (0, 1 versus 2). The primary endpoint was the overall survival (OS) rate at 6 months.

Results: In total, 120 patients were enrolled and 118 patients were randomised (mFOLFOX n = 59, mFOLFIRI n = 59). The baseline characteristics were well balanced between the two arms. The tumour location was intrahepatic bile duct in 48 patients (40.7%), extrahepatic bile duct in 29 patients (24.6%), gallbladder in 35 patients (29.7%) and ampulla of Vater in 6 patients (5.1%). At a median follow-up duration of 25.8 months, the 6-month OS rate was 54.1% in mFOLFOX and 44.1% in mFOLFIRI (p = 0.677). The median OS was 6.3 months (95% CI, 4.4-8.2) in mFOLFOX and 5.7 months (95% CI, 4.7-6.7) in mFOLFIRI (p = 0.677). The median progression-free survival was 2.8 months (95% CI, 2.3-3.3) in mFOLFOX and 2.1 months (95% CI, 1.1-3.1) in mFOLFIRI (p = 0.974). Of the 101 evaluable patients, the objective response rate and disease control rate were 5.9% and 66.7% in mFOLFOX and 4.0% and 64.0% in mFOLFIRI (p = 0.663 and p = 0.778, respectively). Peripheral neuropathy (37.5% versus 5.2%) and thrombocytopenia (35.7% versus 15.5%) in mFOLFOX and vomiting (19.0% versus 1.8%) and cholangitis (10.3% versus 0.0%) in mFOLFIRI occurred more frequently. No chemotherapy-related death was reported.

Conclusion: In the second-line treatment of BTC, mFOLFIRI was not superior to mFOLFOX. However, mFOLFIRI was tolerable and showed comparable efficacy to mFOLFOX. Adverse events were different between the two arms. CLINICALTRIALS.

Gov Identifier: NCT03464968.
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http://dx.doi.org/10.1016/j.ejca.2021.06.019DOI Listing
September 2021

Sequence and analysis of the complete mitochondrial genome of the Eurasian tree sparrow in the Republic of Korea (Passeriformes, Passeridae).

Mitochondrial DNA B Resour 2021 May 19;6(6):1682-1684. Epub 2021 May 19.

Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Gwangju, Korea.

Eurasian Tree Sparrow is widely distributed passerine bird, and one sub-species is known to inhabit North-East Asia. In this study, we decode the complete mitochondrial genome of from the Republic of Korea. Mitogenome was 16,904 bp in length, and the content of A, T, G, and C were 30.0% (5079 bp), 22.5% (3810 bp), 15.5% (2621 bp), and 31.9% (5394 bp), respectively. The circular mitogenome contained 38 genes (13 protein-coding genes, 22 transfer RNAs, and 2 ribosomal RNAs) and a non-coding region. Phylogenetic analysis based on the complete mitogenome sequences indicated genetic distances in the species of Passeriformes, and in the Republic of Korea is included in a monophyletic group with in China. This result provide basic information of population genetics of wide-ranging species Eurasian Tree Sparrow.
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http://dx.doi.org/10.1080/23802359.2021.1927876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143616PMC
May 2021

L1CAM is not associated with extracellular vesicles in human cerebrospinal fluid or plasma.

Nat Methods 2021 06 3;18(6):631-634. Epub 2021 Jun 3.

Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.

L1CAM is a transmembrane protein expressed on neurons that was presumed to be found on neuron-derived extracellular vesicles (NDEVs) in human biofluids. We developed a panel of single-molecule array assays to evaluate the use of L1CAM for NDEV isolation. We demonstrate that L1CAM is not associated with extracellular vesicles in human plasma or cerebrospinal fluid and therefore recommend against its use as a marker in NDEV isolation protocols.
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http://dx.doi.org/10.1038/s41592-021-01174-8DOI Listing
June 2021

Characterizing Smart Environments as Interactive and Collective Platforms: A Review of the Key Behaviors of Responsive Architecture.

Sensors (Basel) 2021 May 14;21(10). Epub 2021 May 14.

School of Architecture, Hanyang University, Seoul 04763, Korea.

Since architect Nicholas Negroponte first proposed a vision of responsive architecture smart environments have been widely investigated, especially in the fields of computer science and engineering. Despite growing interest in the topic, a comprehensive review of research about smart environments from the architectural perspective is largely missing. In order to provide a formal understanding of smart environments in architecture, this paper conducts a systematic literature review of scholarly sources over the last decade, focusing on four related subjects: (1) responsive architecture, (2) kinetic architecture, (3) adaptive architecture and (4) intelligent buildings. Through this review, the paper identifies and examines and behaviors in smart environments, thereby contributing to defining the properties of creative, smart spaces in the contemporary digital ecosystem. In addition, this research offers a means of systematically characterizing and constructing smart environments as and platforms, enabling occupants to sense, experience and understand smart spaces.
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http://dx.doi.org/10.3390/s21103417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156320PMC
May 2021

Lessons Learned from an Experience with Vancomycin-Intermediate Outbreak in a Newly Built Secondary Hospital in Korea.

Pathogens 2021 May 6;10(5). Epub 2021 May 6.

Department of Internal Medicine, Division of Infectious Disease, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si 16995, Korea.

A vancomycin-intermediate (VISA) outbreak occurred in an intensive care unit (ICU) in South Korea. We aimed to investigate the condition that led to the VISA outbreak and seek measures to prevent further spread of the multidrug-resistant organism. A total of three VISA isolates were obtained from two patients and a health care worker (HCW) in a newly built 450-bed secondary hospital. Extensive screening of close contacts for VISA in terms of space sharing and physical contact, irrespective of contact time, was performed. Furthermore, multilocus sequence type, staphylococcal cassette chromosome mec type, and type profiles were determined for all VISA isolates. The relationship between vancomycin use and the minimum inhibitory concentration (MIC) of was also investigated. Molecular typing showed that the strains of the three VISA isolates were identical, indicating horizontal hospital transmission. We assumed that VISA colonised in the HCW could have transmitted to the two patients, which resulted in one infection and one colonisation. The affected HCW was excused from work and was decolonised with mupirocin. Five weeks after the interventions, no additional VISA isolates were identified. No relationship between vancomycin use and MIC of was identified. Extensive screening of contacts in addition to decolonisation is crucial in preventing the further spread of VISA.
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http://dx.doi.org/10.3390/pathogens10050564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148553PMC
May 2021

Spatiotemporal contribution of neuromesodermal progenitor-derived neural cells in the elongation of developing mouse spinal cord.

Life Sci 2021 Oct 15;282:119393. Epub 2021 May 15.

Department of Anatomy and Division of Brain, Korea 21 Plus Program for Biomedical Science, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, Seoul 02841, Republic of Korea. Electronic address:

Aims: During vertebrate development, the posterior end of the embryo progressively elongates in a head-to-tail direction to form the body plan. Recent lineage tracing experiments revealed that bi-potent progenitors, called neuromesodermal progenitors (NMPs), produce caudal neural and mesodermal tissues during axial elongation. However, their precise location and contribution to spinal cord development remain elusive.

Main Methods: Here we used NMP-specific markers (Sox2 and BraT) and a genetic lineage tracing system to localize NMP progeny in vivo.

Key Findings: Sox2 and BraT double positive cells were initially located at the tail tip, but were later found in the caudal neural tube, which is a unique feature of mouse development. In the neural tube, they produced neural progenitors (NPCs) and contributed to the spinal cord gradually along the AP axis during axial elongation. Interestingly, NMP-derived NPCs preferentially contributed to the ventral side first and later to the dorsal side at the lumbar spinal cord level, which may be associated with atypical junctional neurulation in mice.

Significance: Our current observations detail the contribution of NMP progeny to spinal cord elongation and provide insights into how different species uniquely execute caudal morphogenesis.
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http://dx.doi.org/10.1016/j.lfs.2021.119393DOI Listing
October 2021

Embryonal Neuromesodermal Progenitors for Caudal Central Nervous System and Tissue Development.

J Korean Neurosurg Soc 2021 May 26;64(3):359-366. Epub 2021 Apr 26.

Department of Anatomy, Brain Korea 21 Plus Program for Biomedical Science, Korea University College of Medicine, Seoul, Korea.

Neuromesodermal progenitors (NMPs) constitute a bipotent cell population that generates a wide variety of trunk cell and tissue types during embryonic development. Derivatives of NMPs include both mesodermal lineage cells such as muscles and vertebral bones, and neural lineage cells such as neural crests and central nervous system neurons. Such diverse lineage potential combined with a limited capacity for self-renewal, which persists during axial elongation, demonstrates that NMPs are a major source of trunk tissues. This review describes the identification and characterization of NMPs across multiple species. We also discuss key cellular and molecular steps for generating neural and mesodermal cells for building up the elongating trunk tissue.
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http://dx.doi.org/10.3340/jkns.2020.0359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128519PMC
May 2021

4-CMTB Ameliorates Ovalbumin-Induced Allergic Asthma through FFA2 Activation in Mice.

Biomol Ther (Seoul) 2021 Jul;29(4):427-433

Laboratory of Pharmacology, College of Pharmacy, and Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

Free fatty acid receptor 2 (FFA2, also known as GPR43), a G-protein-coupled receptor, has been known to recognize short-chain fatty acids and regulate inflammatory responses. FFA2 gene deficiency exacerbated disease states in several models of inflammatory conditions including asthma. However, efficacy of FFA2 agonists has not been tested in allergic asthma. Thus, we investigated effect of 4-chloro-α-(1-methylethyl)--2-thiazoylylbenzeneacetanilide (4-CMTB), a FFA2 agonist, on antigen-induced degranulation in RBL-2H3 cells and ovalbumin-induced allergic asthma in BALB/c mice. Treatment of 4-CMTB inhibited the antigen-induced degranulation concentration-dependently. Administration of 4-CMTB decreased the immune cell numbers in the bronchoalveolar lavage fluid and suppressed the expression of inflammatory Th2 cytokines (IL-4, IL-5, and IL-13) in the lung tissues. Histological studies revealed that 4-CMTB suppressed mucin production and inflammation in the lungs. Thus, results proved that FFA2 functions to suppress allergic asthma, suggesting 4-CMTB activation of FFA2 as a therapeutic tool for allergic asthma.
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http://dx.doi.org/10.4062/biomolther.2020.176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255137PMC
July 2021

Korean Red Ginseng reduces chronic social defeat stress-induced mood disorders via N-methyl-D-aspartate receptor modulation in mice.

J Ginseng Res 2021 Mar 7;45(2):254-263. Epub 2019 Nov 7.

Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.

Background: A chronic social defeat stress (CSDS) model has been proposed as relevant to stress-induced behavioral change in humans. In this study, we examined the effect of Korean Red Ginseng (KRG) on CSDS-induced mood disorders and protein expression in an animal model.

Methods: To evaluate the effect of KRG on social defeat stress, test mice were exposed in the resident aggressor's home cage compartment for 14 days beginning 1 h after KRG treatment (10, 20, and 40 mg/kg, per oral (p.o.)). After the exposure, behavioral tests to measure anxiety, social interaction, and depression-like behavior were performed. To investigate the underlying mechanism, N-methyl-D-aspartate receptor expression levels in CSDS-induced mice were evaluated using Western blot analysis.

Results: CSDS induced anxiety-like behaviors by decreasing central activity in the open-field test and open-arm approach in the elevated plus maze test and led to social avoidance behavior in the social interaction test. CSDS mice showed upregulated NR1, NR2A, and NR2B expression in the hippocampus. KRG 20 and 40 mg/kg ameliorated anxiety-like activities and KRG 20 mg/kg alleviated social avoidance by decreasing time in the corner zone. KRG treatment recovered CSDS-induced NR1, NR2A, and NR2B protein levels in the hippocampus.

Conclusion: These results indicate that KRG has a therapeutic effect on CSDS-induced mood disorder by alleviating N-methyl-D-aspartate receptor overexpression in the hippocampus.
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http://dx.doi.org/10.1016/j.jgr.2019.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020286PMC
March 2021

Rapid and Efficient Generation of Myelinating Human Oligodendrocytes in Organoids.

Front Cell Neurosci 2021 17;15:631548. Epub 2021 Mar 17.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia.

Human stem cell derived brain organoids are increasingly gaining attention as an ideal model system for investigating neurological diseases, particularly those that involve myelination defects. However, current protocols for generating brain organoids with sufficiently mature oligodendrocytes that deposit myelin on endogenously produced neurons are lengthy and complicated. Taking advantage of a human pluripotent stem cell line that reports on SOX10 expression, we developed a protocol that involves a 42 day exposure of neuroectoderm-derived organoids to a cocktail of growth factors and small molecules that collectively foster oligodendrocyte specification and survival. Importantly, the resulting day 42 brain organoids contain both myelinating oligodendrocytes, cortical neuronal cells and astrocytes. These oligodendrocyte brain organoids therefore constitute a valuable and tractable platform for functional neurogenomics and drug screening for white matter diseases.
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http://dx.doi.org/10.3389/fncel.2021.631548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010307PMC
March 2021

Efficacy and safety of Soshiho-tang in atopic dermatitis patients with gastrointestinal disorders: A double-blinded, randomized, and placebo-controlled clinical trial.

J Ethnopharmacol 2021 Jun 23;274:114006. Epub 2021 Mar 23.

Department of Korean Medicine Ophthalmology and Otolaryngology and Dermatology, Wonkwang University Korean Medicine Hospital and Research Center of Traditional Korean Medicine, Wonkwang University, Iksan, Jeollabuk-do, Republic of Korea. Electronic address:

Ethnopharmacological Relevance: Because of the growing incidence of AD, psychosocial and economic burden of AD patients are often considerable. Steroid treatments are widely used, but long term use of this treatment can cause side effects. To reduce the burden of AD patients and find new efficient treatment, this study chose Soshiho-tang, a traditional medicine used in eastern Asia.

Aim Of The Study: Soshiho-tang (SSHT) is a traditional herbal medicine that has anti-inflammatory effects and improves immune function. This clinical trial evaluated the efficacy and safety of SSHT in atopic dermatitis (AD) patients with gastrointestinal disorders in comparison with placebo.

Materials And Methods: This study was a single-center, randomized, double-blinded, placebo-controlled, and investigator-initiated clinical trial. A total of 60 patients aged 3-18 years with gastrointestinal disorders and diagnosed with AD by Hanifin & Rajka criteria with a Scoring Atopic Dermatitis (SCORAD) index between 15 and 49 were enrolled. Participants were randomly assigned to the SSHT or placebo groups in a ratio of 1:1 and efficacy evaluation was conducted at week 4 and 8. The participants orally administered SSHT or placebo three times a day for 4 weeks. The primary outcome was measured based on a change of SCORAD index. The secondary outcome measurements included the following: survey questionnaires of gastrointestinal disorder, amount and frequency of ointment application for AD, dermatology quality of life index, and safety evaluation (diagnostic test, adverse reaction, and vital sign monitoring).

Results: During efficacy evaluation, the SCORAD score and digestive symptoms in the experimental and placebo groups were not statistically significant. However, the amount and frequency of ointment application in the experimental group were reduced compared to those in the placebo group at week 8. Also, In the Children's Dermatology Life Quality Index (CDLQI), statistically significant Quality of Life (QOL) improvement was observed in the SSHT experimental group compared to the placebo group. In safety evaluation, all participants were within the normal range during the study period. Blood sample testing indicated that the lymphocytes ratio decreased, and neutrophils ratio increased in the experimental group, whereas the placebo group showed the opposite immune response pattern.

Conclusion: We concluded that SSHT administration can reduce steroid ointment dependence and improve the QOL in AD patients by regulating neutrophil-lymphocyte ratio.
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http://dx.doi.org/10.1016/j.jep.2021.114006DOI Listing
June 2021

Neurodevelopmental defects and neurodegenerative phenotypes in human brain organoids carrying Parkinson's disease-linked mutations.

Sci Adv 2021 Feb 17;7(8). Epub 2021 Feb 17.

Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Republic of Korea.

Loss-of-function mutations of , encoding HSP40 auxilin, have recently been identified in patients with early-onset Parkinson's disease (PD). To study the roles of DNAJC6 in PD pathogenesis, we used human embryonic stem cells with CRISPR-Cas9-mediated gene editing. Here, we show that mutations cause key PD pathologic features, i.e., midbrain-type dopamine (mDA) neuron degeneration, pathologic α-synuclein aggregation, increase of intrinsic neuronal firing frequency, and mitochondrial and lysosomal dysfunctions in human midbrain-like organoids (hMLOs). In addition, neurodevelopmental defects were also manifested in hMLOs carrying the mutations. Transcriptomic analyses followed by experimental validation revealed that defects in DNAJC6-mediated endocytosis impair the WNT-LMX1A signal during the mDA neuron development. Furthermore, reduced expression during development caused the generation of vulnerable mDA neurons with the pathologic manifestations. These results suggest that the human model of -PD recapitulates disease phenotypes and reveals mechanisms underlying disease pathology, providing a platform for assessing therapeutic interventions.
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http://dx.doi.org/10.1126/sciadv.abb1540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888924PMC
February 2021

TRITC-Loaded PLGA Nanoparticles as Drug Delivery Carriers in Mouse Oocytes and Embryos.

ACS Appl Mater Interfaces 2021 Feb 27;13(5):5975-5988. Epub 2021 Jan 27.

Department of Biomedical Science, College of Life Science, CHA University, 6F, CHA Biocomplex, Sampyeong-Dong, Bundang-gu, Seongnam-si 13488, Republic of Korea.

The structural layers around oocytes make it difficult to deliver drugs aimed at treating infertility. In this study, we sought to identify nanoparticles (NPs) that could easily pass through zona pellucida (ZP), a special layer around oocytes, for use as a drug delivery carrier. Three types of NPs were tested: quantum dot NPs, PE-polyethylene glycol (PEG)-loaded poly(lactic--glycolic acid) (PLGA) NPs (PEG/PL), and tetramethylrhodamine-loaded PLGA NPs (TRNPs). When mouse oocytes were treated with NPs, only TRNPs could fully pass through the ZP and cell membrane. To assess the effects of TRNPs on fertility and potential nanotoxicity, we performed mRNA sequencing analysis to confirm their genetic safety. We established a system to successfully internalize TRNPs into oocytes. The genetic stability and normal development of TRNP-treated oocytes and embryos were confirmed. These results imply that TRNPs can be used as a drug delivery carrier applicable to germ cells.
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http://dx.doi.org/10.1021/acsami.0c19792DOI Listing
February 2021

3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics.

Nat Commun 2021 01 21;12(1):492. Epub 2021 Jan 21.

Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.

Investigation of neural circuit dynamics is crucial for deciphering the functional connections among regions of the brain and understanding the mechanism of brain dysfunction. Despite the advancements of neural circuit models in vitro, technologies for both precisely monitoring and modulating neural activities within three-dimensional (3D) neural circuit models have yet to be developed. Specifically, no existing 3D microelectrode arrays (MEAs) have integrated capabilities to stimulate surrounding neurons and to monitor the temporal evolution of the formation of a neural network in real time. Herein, we present a 3D high-density multifunctional MEA with optical stimulation and drug delivery for investigating neural circuit dynamics within engineered 3D neural tissues. We demonstrate precise measurements of synaptic latencies in 3D neural networks. We expect our 3D multifunctional MEA to open up opportunities for studies of neural circuits through precise, in vitro investigations of neural circuit dynamics with 3D brain models.
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http://dx.doi.org/10.1038/s41467-020-20763-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820464PMC
January 2021

Tumor LAG-3 and NY-ESO-1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non-small cell lung cancer.

Thorac Cancer 2021 03 17;12(5):619-630. Epub 2021 Jan 17.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.

Background: Immune checkpoint inhibitors (ICIs) are an established treatment for non-small cell lung cancer (NSCLC) that have demonstrated durable clinical benefits (DCBs). Previous studies have suggested NY-ESO-1 and LAG-3 to be surrogate markers of ICI responses in NSCLC; therefore, we explored the predictive value of their expression in NSCLC.

Methods: We retrospectively reviewed the records of 38 patients with advanced NSCLC treated with anti-PD-1 monoclonal antibodies from 2013 to 2016 at Seoul National University Hospital and Seoul National University Bundang Hospital after failed platinum-based chemotherapy. Tumor tissues from each patient were subjected to immunohistochemical analysis to determine NY-ESO-1, LAG-3, and PD-L1 expression, whose ability to predict progression-free survival (PFS) and overall survival (OS) was then analyzed alongside their positive (PPV) and negative (NPV) predictive values.

Results: NY-ESO-1 or LAG-3 expression was detected in all tumor samples from patients with high PD-L1 expression and was significantly associated with favorable outcomes, unlike PD-L1 expression. Patients with both NY-ESO-1- and LAG-3-expressing tumors had a high DCB rate and those with triple-positive PD-L1, LAG-3, and NY-ESO expression had a superior median OS and PFS than those with triple-negative expression. Furthermore, LAG-3 and NY-ESO-1 co-expression was an independent predictor of both PFS and OS, while LAG-3 displayed a good NPV.

Conclusions: Patients with NSCLC who co-express NY-ESO-1 or LAG-3 with PD-L1 exhibit greater DCBs and improved long-term survival following anti-PD-1 therapy. Moreover, NY-ESO-1 and LAG-3 could be novel predictive biomarkers of survival and should be considered in the future use of ICIs.
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http://dx.doi.org/10.1111/1759-7714.13834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919166PMC
March 2021

Efficacy and Safety of Socheongryong-Tang Among Atopic Dermatitis Patients With Respiratory Disorders: A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial.

Front Pharmacol 2020 26;11:597885. Epub 2020 Nov 26.

Department of Korean Medicine Ophthalmology and Otolaryngology and Dermatology, Wonkwang University Korean Medicine Hospital and Research Center of Traditional Korean Medicine, Wonkwang University, Iksan, South Korea.

Atopic dermatitis is a chronic inflammatory skin disease that affects the growth and development of children. The prevalence of atopic dermatitis has been continually increasing, and this has also been accompanied by rising socioeconomic costs. Interest has been growing in alternative medicine as a means of alleviating the burden of atopic dermatitis. This was a single-center, double-blinded, randomized, placebo-controlled investigator-led clinical trial including 60 atopic dermatitis patients. The participants were classified into an experimental group (30 persons) and a control group (30 persons), who were administered, respectively, socheongryong-tang or a placebo for 4 weeks. After 4 weeks of treatment, the participants visited the trial center again and assess their efficacy and safety. The researchers performed statistical comparisons of the changes in the SCORAD Index, amount and frequency of ointment use, and height and weight to assess the efficacy. To assess the safety, diagnostic tests and vital sign checks were performed at each visit, and the presence or absence of adverse events was observed. As a result, the frequency and the amount of steroid ointment application in both groups increased, but the experimental group showed less tendency ( = 0.081). Results of analyzing the children in the experimental group in relation to growth showed a significantly greater height growth than the control group ( < 0.05). In addition, all study participants did not show any remarkable abnormal signs in the safety evaluation. In conclusion, compared to the control group, the experimental group, who took socheongryong-tang showed a tendency to be less dependent on steroid ointment and statistically significant increase in height.
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http://dx.doi.org/10.3389/fphar.2020.597885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726431PMC
November 2020

Endosomal Dysfunction Induced by Directly Overactivating Rab5 Recapitulates Prodromal and Neurodegenerative Features of Alzheimer's Disease.

Cell Rep 2020 11;33(8):108420

Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Department of Psychiatry, New York University Langone Health, New York, NY 10016, USA; Department of Cell Biology, New York University Langone Health, New York, NY 10003, USA; NYU Neuroscience Institute, New York, NY 10003, USA. Electronic address:

Neuronal endosomal dysfunction, the earliest known pathobiology specific to Alzheimer's disease (AD), is mediated by the aberrant activation of Rab5 triggered by APP-β secretase cleaved C-terminal fragment (APP-βCTF). To distinguish pathophysiological consequences specific to overactivated Rab5 itself, we activate Rab5 independently from APP-βCTF in the PA-Rab5 mouse model. We report that Rab5 overactivation alone recapitulates diverse prodromal and degenerative features of AD. Modest neuron-specific transgenic Rab5 expression inducing hyperactivation of Rab5 comparable to that in AD brain reproduces AD-related Rab5-endosomal enlargement and mistrafficking, hippocampal synaptic plasticity deficits via accelerated AMPAR endocytosis and dendritic spine loss, and tau hyperphosphorylation via activated glycogen synthase kinase-3β. Importantly, Rab5-mediated endosomal dysfunction induces progressive cholinergic neurodegeneration and impairs hippocampal-dependent memory. Aberrant neuronal Rab5-endosome signaling, therefore, drives a pathogenic cascade distinct from β-amyloid-related neurotoxicity, which includes prodromal and neurodegenerative features of AD, and suggests Rab5 overactivation as a potential therapeutic target.
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http://dx.doi.org/10.1016/j.celrep.2020.108420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714675PMC
November 2020

Prevention of mitochondrial impairment by inhibition of protein phosphatase 1 activity in amyotrophic lateral sclerosis.

Cell Death Dis 2020 10 21;11(10):888. Epub 2020 Oct 21.

Department of Anatomy, Korea University College of Medicine, Brain Korea 21 plus, Seoul, 02841, Republic of Korea.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by progressive loss of motor neurons (MNs) and subsequent muscle weakness. These pathological features are associated with numerous cellular changes, including alteration in mitochondrial morphology and function. However, the molecular mechanisms associating mitochondrial structure with ALS pathology are poorly understood. In this study, we found that Dynamin-related protein 1 (Drp1) was dephosphorylated in several ALS models, including those with SOD1 and TDP-43 mutations, and the dephosphorylation was mediated by the pathological induction of protein phosphatase 1 (PP1) activity in these models. Suppression of the PP1-Drp1 cascade effectively prevented ALS-related symptoms, including mitochondrial fragmentation, mitochondrial complex I impairment, axonal degeneration, and cell death, in primary neuronal culture models, iPSC-derived human MNs, and zebrafish models in vivo. These results suggest that modulation of PP1-Drp1 activity may be a therapeutic target for multiple pathological features of ALS.
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http://dx.doi.org/10.1038/s41419-020-03102-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578657PMC
October 2020

Anteroposterior Wnt-RA Gradient Defines Adhesion and Migration Properties of Neural Progenitors in Developing Spinal Cord.

Stem Cell Reports 2020 10 24;15(4):898-911. Epub 2020 Sep 24.

Department of Anatomy, Brain Korea 21 Plus Program, Korea University College of Medicine, Seoul, 02841, Korea. Electronic address:

Mammalian embryos exhibit a transition from head morphogenesis to trunk elongation to meet the demand of axial elongation. The caudal neural tube (NT) is formed with neural progenitors (NPCs) derived from neuromesodermal progenitors localized at the tail tip. However, the molecular and cellular basis of elongating NT morphogenesis is yet elusive. Here, we provide evidence that caudal NPCs exhibit strong adhesion affinity that is gradually decreased along the anteroposterior (AP) axis in mouse embryonic spinal cord and human cellular models. Strong cell-cell adhesion causes collective migration, allowing AP alignment of NPCs depending on their birthdate. We further validated that this axial adhesion gradient is associated with the extracellular matrix and is under the control of graded Wnt signaling emanating from tail buds and antagonistic retinoic acid (RA) signaling. These results suggest that progressive reduction of NPC adhesion along the AP axis is under the control of Wnt-RA molecular networks, which is essential for a proper elongation of the spinal cord.
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http://dx.doi.org/10.1016/j.stemcr.2020.08.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562945PMC
October 2020

Gamma secretase inhibition impairs HCMV replication by reduction of immediate early gene expression at the transcriptional level.

Antiviral Res 2020 11 2;183:104867. Epub 2020 Aug 2.

College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea. Electronic address:

Due to diverse pathogenic potentials, there is a growing need for anti-HCMV agents. In this study, we show that treatment with DAPT, a γ-secretase inhibitor (GSI), impairs HCMV replication as assessed by a progeny assay based on immunostaining. This effect is not limited to DAPT because other GSIs with different structures and distinct mechanisms of action also exhibit a similar level of inhibitory effects on HCMV viral production, indicating that γ-secretase activity is required for efficient HCMV replication. Western blot and qPCR analyses reveal that DAPT does not interfere with the viral entry process, but reduces expression of the immediate early protein IE1 at the transcriptional level. Furthermore, we exclude the possible involvement of Notch signaling pathway during HCMV replication by showing that expression of the dominant-negative form of MAML1, which disrupts the transactivational ability of Notch intracellular domain (NICD), does not reduce viral particle formation, and that NICD cannot rescue the DAPT-treated outcomes. Taken together, these findings indicate that γ-secretase activity plays an important role in a key step of the HCMV life cycle and γ-secretase inhibition could potentially be used as a novel preventive and therapeutic strategy against HCMV infection and HCMV-related diseases.
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http://dx.doi.org/10.1016/j.antiviral.2020.104867DOI Listing
November 2020

YAP Enhances FGF2-Dependent Neural Stem Cell Proliferation by Induction of FGF Receptor Expression.

Stem Cells Dev 2020 09 12;29(18):1240-1246. Epub 2020 Aug 12.

College of Biotechnology and Bioengineering, Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of Korea.

The Hippo signaling pathway regulates cell proliferation and organ growth, and its activation is mainly reflected by the phosphorylation levels of Yes-associated protein (YAP). In this study, we show that YAP facilitates embryonic neural stem cell proliferation by elevating their responsiveness to fibroblast growth factor 2 (FGF2), one of the major growth factors for neural stem cells, in vivo as well as in vitro. Western blot and quantitative real-time PCR analyses revealed that expression of the FGF receptors (FGFRs) to were greatly increased by YAP expression upon FGF2 treatment, followed by upregulation of the mitogen-activated protein kinase and protein kinase B signaling pathways. Furthermore, as assessed by quantitative real-time PCR analyses, YAP-induced expression was found to be TEA domain transcription factor (TEAD)-independent, and transcriptional coactivator with PDZ-binding motif, the other homolog of Yorki in the Hippo signaling pathway, was found to possess similar activity to YAP. Finally, adjustment of FGFR signaling activity in the YAP-expressing cells to control levels efficiently offset the cell proliferative effects of YAP, suggesting that the increased proliferation of YAP-expressing neural stem cells was mainly attributable to enhanced FGFR signaling. Our data indicate that YAP plays an important role in neural stem cell regulation by elevating FGFR expression, subsequently leading to enhanced cell proliferation.
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http://dx.doi.org/10.1089/scd.2019.0281DOI Listing
September 2020

Topical Application of S1P Antagonist JTE-013 Attenuates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice.

Biomol Ther (Seoul) 2020 Nov;28(6):537-541

Laboratory of Pharmacology, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.

Sphingosine-1-phosphate (S1P) and its receptors have been implicated in atopic dermatitis. S1P2 was found to function as a proallergic receptor, while its antagonist JTE-013 was found to suppress allergic asthma in mice. Topical application of JTE-013 has not been investigated in an model of atopic dermatitis. Therefore, the therapeutic potential of JTE-013 topical application was evaluated by the use of a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model. DNCB-induced inflammation and mast cell accumulation in skin tissues were significantly suppressed by topical JTE-013 treatment in BALB/c mice. DNCB-induced increase of lymph nodes sizes and elevated inflammatory cytokines (IL-4, IL-13, IL-17, and IFN-γ) in lymph nodes were also significantly reduced by the JTE-013 treatment. Elevated serum levels of IgE were significantly suppressed by the topical treatment of JTE-013. In summary, the topical treatment of JTE-013 S1P antagonist suppressed DNCB-induced atopic dermatitis symptoms and immune responses. These results suggested JTE-013 as a potential therapeutic agent for atopic dermatitis.
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http://dx.doi.org/10.4062/biomolther.2020.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585635PMC
November 2020

Factors Associated with Molar-Incisor Hypomineralization: A Population-Based Case-Control Study.

Pediatr Dent 2020 Mar;42(2):134-140

Dr. Y. M. Yang is a professor, Department of Pediatric Dentistry, School of Dentistry, Jeonbuk National University and Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea;, Email:

The purpose of this case-control study was to investigate the relationship between molar-incisor hypomineralization (MIH) and pre-, peri-, and postnatal conditions of children and mothers in South Korea. The Korean Academy of Pediatric Dentistry con- ducted this study to examine factors associated with MIH among six- to 13-year-olds. The European Academy of Pediatric Dentistry criteria and self-administered questionnaires associated with MIH were used. In multivariable logistic regression analysis, the odds ratio (OR) of MIH for children whose mothers used health supplements during pregnancy was 0.65 (P=0.009). Also, children with more than three hours of out- door activities per day tended to have a lower MIH (P=0.03) than did those with zero hours of outdoor activity. Additionally, the OR of MIH for children whose mothers smoked during pregnancy was 2.37 (P=0.019) and the MIH found to be 1.33 times more frequent in children with respiratory infections during the first three years of life (P=0.048). Maternal smoking during pregnancy and child's pediatric respiratory infection suffered within three years after birth are factors associated with the MIH among Korean children. Further study is needed because the prevalence of MIH in children whose mothers taking health supplements (vitamins or folic acid or iron) during pregnancy is low.
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March 2020

Polypharmacy, Inappropriate Medication Use, and Drug Interactions in Older Korean Patients with Cancer Receiving First-Line Palliative Chemotherapy.

Oncologist 2020 03 27;25(3):e502-e511. Epub 2019 Nov 27.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.

Background: Polypharmacy is an important issue in the care of older patients with cancer, as it increases the risk of unfavorable outcomes. We estimated the prevalence of polypharmacy, potentially inappropriate medication (PIM) use, and drug-drug interactions (DDIs) in older patients with cancer in Korea and their associations with clinical outcomes.

Subjects, Materials, And Methods: This was a secondary analysis of a prospective observational study of geriatric patients with cancer undergoing first-line palliative chemotherapy. Eligible patients were older adults (≥70 years) with histologically diagnosed solid cancer who were candidates for first-line palliative chemotherapy. All patients enrolled in this study received a geriatric assessment (GA) at baseline. We reviewed the daily medications taken by patients at the time of GA before starting chemotherapy. PIMs were assessed according to the 2015 Beers criteria, and DDIs were assessed by a clinical pharmacist using Lexi-comp Drug Interactions. We evaluated the association between polypharmacy and clinical outcomes including treatment-related toxicity, and hospitalization using logistic regression and Cox regression analyses.

Results: In total, 301 patients (median age 75 years; range, 70-93) were enrolled; the most common cancer types were colorectal cancer (28.9%) and lung cancer (24.6%). Mean number of daily medications was 4.7 (±3.1; range, 0-14). The prevalence of polypharmacy (≥5 medications) was 45.2% and that of excessive polypharmacy (≥10 medications) was 8.6%. PIM use was detected in 137 (45.5%) patients. Clinically significant DDIs were detected in 92 (30.6%) patients. Polypharmacy was significantly associated with hospitalization or emergency room (ER) visits (odds ratio: 1.73 [1.18-2.55], p < .01). Neither polypharmacy nor PIM use showed association with treatment-related toxicity.

Conclusion: Polypharmacy, PIM use, and potential major DDIs were prevalent in Korean geriatric patients with cancer. Polypharmacy was associated with a higher risk of hospitalization or ER visits during the chemotherapy period.

Implications For Practice: This study, which included 301 older Korean patients with cancer, highlights the increased prevalence of polypharmacy in this population planning to receive palliative chemotherapy. The prevalence of polypharmacy and excessive polypharmacy was 45.2% and 8.6%, respectively. The prescription of potentially inappropriate medications (PIMs) was detected in 45.5% and clinically significant drug-drug interaction in 30.6% of patients. Given the association of polypharmacy with increased hospitalization or emergency room visits, this study points to the need for increased awareness and intervention to minimize polypharmacy in the geriatric cancer population undergoing chemotherapy. Moreover, specific criteria for establishing PIMs should be adopted for the treatment of older adults with cancer.
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http://dx.doi.org/10.1634/theoncologist.2019-0085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066695PMC
March 2020

Ethylparaben induces apoptotic cell death in human placenta BeWo cells via the Caspase-3 pathway.

Anim Cells Syst (Seoul) 2020 9;24(1):34-43. Epub 2020 Jan 9.

Department of Life Science, Chung-Ang University, Seoul, South Korea.

Parabens are generally used as preservatives in foods, pharmaceuticals, and various other commercial products. Among them, ethylparaben has weaker estrogenic characteristics than endogenous estrogen. However, growing evidence indicates that ethylparaben has an adverse effect on various human tissues. Here, we investigated whether ethylparaben induces cell death by affecting cell viability, cell proliferation, cell cycle, and apoptosis using the human placenta cell line BeWo. Ethylparaben significantly decreased cell viability in a dose-dependent manner. It caused cell cycle arrest at sub-G1 by reducing the expression of cyclin D1, whereas it decreased the cell proportion at the G0/G1 and S phases. Furthermore, we verified that ethylparaben induces apoptotic cell death by enhancing the activity of Caspase-3. Taken together, our results suggest that ethylparaben exerts cytotoxic effects in human placental BeWo cells via cell cycle arrest and apoptotic pathways.
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http://dx.doi.org/10.1080/19768354.2020.1711804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048193PMC
January 2020

A microfluidic gradient device for drug screening with human iPSC-derived motoneurons.

Analyst 2020 Apr 9;145(8):3081-3089. Epub 2020 Mar 9.

Department of Biomedical Engineering, Sogang University, Seoul, Korea.

We developed a microfluidic gradient device to utilize as a drug screening system with human induced pluripotent stem cell (hiPSC)-derived motoneurons. The microfluidic channel was asymmetrically designed to generate the concentration gradients and a micropillar array was used to trap and culture the motoneuron spheroids containing motoneurons for 9 days. We optimized the concentration gradients in the microfluidic device using a computational fluid dynamics (CFD) model. We also observed that the motoneuron spheroid-derived neurite network was generated in response to the concentration gradients of riluzole in the microfluidic device. Therefore, this microfluidic gradient device could be useful for screening of various drugs for neurological disease applications.
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http://dx.doi.org/10.1039/c9an02384dDOI Listing
April 2020

β2-adrenergic Agonists Rescue Lysosome Acidification and Function in PSEN1 Deficiency by Reversing Defective ER-to-lysosome Delivery of ClC-7.

J Mol Biol 2020 04 24;432(8):2633-2650. Epub 2020 Feb 24.

Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, 10962, USA; Department of Psychiatry, Langone Medical Center, New York, NY, 10016, USA; Department of Cell Biology, Langone Medical Center, New York, NY, 10016, USA; Neuroscience Institute, New York University, New York, NY 10016, USA. Electronic address:

Lysosomal dysfunction is considered pathogenic in Alzheimer disease (AD). Loss of presenilin-1 (PSEN1) function causing AD impedes acidification via defective vacuolar ATPase (vATPase) V0a1 subunit delivery to lysosomes. We report that isoproterenol (ISO) and related β2-adrenergic agonists reacidify lysosomes in PSEN1 Knock out (KO) cells and fibroblasts from PSEN1 familial AD patients, which restores lysosomal proteolysis, calcium homeostasis, and normal autophagy flux. We identify a novel rescue mechanism involving Portein Kinase A (PKA)-mediated facilitation of chloride channel-7 (ClC-7) delivery to lysosomes which reverses markedly lowered chloride (Cl) content in PSEN1 KO lysosomes. Notably, PSEN1 loss of function impedes Endoplasmic Reticulum (ER)-to-lysosome delivery of ClC-7. Transcriptomics of PSEN1-deficient cells reveals strongly downregulated ER-to-lysosome transport pathways and reversibility by ISO, thus accounting for lysosomal Cl deficits that compound pH elevation due to deficient vATPase and its rescue by β2-adrenergic agonists. Our findings uncover a broadened PSEN1 role in lysosomal ion homeostasis and novel pH modulation of lysosomes through β2-adrenergic regulation of ClC-7, which can potentially be modulated therapeutically.
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http://dx.doi.org/10.1016/j.jmb.2020.02.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211125PMC
April 2020

Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson's disease modeling.

Stem Cells 2020 06 28;38(6):727-740. Epub 2020 Feb 28.

School of Biotechnology and Healthcare, Wuyi University, Jiangmen, People's Republic of China.

Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells, including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson's disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD.
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http://dx.doi.org/10.1002/stem.3163DOI Listing
June 2020
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