Publications by authors named "Hee Won Lee"

13 Publications

  • Page 1 of 1

Multiplexed targeting of miRNA-210 in stem cell-derived extracellular vesicles promotes selective regeneration in ischemic hearts.

Exp Mol Med 2021 Apr 20;53(4):695-708. Epub 2021 Apr 20.

Department of Biology Education, College of Education, Pusan National University, Busan, Republic of Korea.

Extracellular vesicles (EVs) are cell derivatives containing diverse cellular molecules, have various physiological properties and are also present in stem cells used for regenerative therapy. We selected a "multiplexed target" that demonstrates multiple effects on various cardiovascular cells, while functioning as a cargo of EVs. We screened various microRNAs (miRs) and identified miR-210 as a candidate target for survival and angiogenic function. We confirmed the cellular and biological functions of EV-210 (EVs derived from ASC) secreted from adipose-derived stem cells (ASCs) transfected with miR-210 (ASC). Under hypoxic conditions, we observed that ASC inhibits apoptosis by modulating protein tyrosine phosphatase 1B (PTP1B) and death-associated protein kinase 1 (DAPK1). In hypoxic endothelial cells, EV-210 exerted its angiogenic capacity by inhibiting Ephrin A (EFNA3). Furthermore, EV-210 enhanced cell survival under the control of PTP1B and induced antiapoptotic effects in hypoxic H9c2 cells. In cardiac fibroblasts, the fibrotic ratio was reduced after exposure to EV-210, but EVs derived from ASC did not communicate with fibroblasts. Finally, we observed the functional restoration of the ischemia/reperfusion-injured heart by maintaining the intercommunication of EVs and cardiovascular cells derived from ASC. These results suggest that the multiplexed target with ASC is a useful tool for cardiovascular regeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s12276-021-00584-0DOI Listing
April 2021

COVID-19 and Adverse Pregnancy Outcome: A Systematic Review of 104 Cases.

J Clin Med 2020 Oct 26;9(11). Epub 2020 Oct 26.

Department of Pediatrics, Yonsei University College of Medicine, Seoul 03722, Korea.

(1) Background: Until now, several reports about pregnant women with confirmed coronavirus disease 2019 (COVID-19) have been published. However, there are no comprehensive systematic reviews collecting all case series studies on data regarding adverse pregnancy outcomes, especially association with treatment modalities. (2) Objective: We aimed to synthesize the most up-to-date and relevant available evidence on the outcomes of pregnant women with laboratory-confirmed infection with COVID-19. (3) Methods: PubMed, Scopus, MEDLINE, Google scholar, and Embase were explored for studies and papers regarding pregnant women with COVID-19, including obstetrical, perinatal, and neonatal outcomes and complications published from 1 January 2020 to 4 May 2020. Systematic review and search of the published literature was done using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). (4) Results: In total, 11 case series studies comprising 104 pregnant women with COVID-19 were included in our review. Fever (58.6%) and cough (30.7%) were the most common symptoms. Other symptoms included dyspnea (14.4%), chest discomfort (3.9%), sputum production (1.0%), sore throat (2.9%), and nasal obstruction (1.0%). Fifty-two patients (50.0%) eventually demonstrated abnormal chest CT, and of those with ground glass opacity (GGO), 23 (22.1%) were bilateral and 10 (9.6%) were unilateral. The most common treatment for COVID-19 was administration of antibiotics (25.9%) followed by antivirals (17.3%). Cesarean section was the mode of delivery for half of the women (50.0%), although no information was available for 28.8% of the cases. Regarding obstetrical and neonatal outcomes, fetal distress (13.5%), pre-labor rupture of membranes (9.6%), prematurity (8.7%), fetal death (4.8%), and abortion (2.9%) were reported. There are no positive results of neonatal infection by RT-PCR. (5) Conclusions: Although we have found that pregnancy with COVID-19 has significantly higher maternal mortality ratio compared to that of pregnancy without the disease, the evidence is too weak to state that COVID-19 results in poorer maternal outcome due to multiple factors. The number of COVID-19 pregnancy outcomes was not large enough to draw a conclusion and long-term outcomes are yet to be determined as the pandemic is still unfolding. Active and intensive follow-up is needed in order to provide robust data for future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9113441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692613PMC
October 2020

Antagonistic interaction between central glucagon-like Peptide-1 and oxytocin on diet-induced obesity mice.

Heliyon 2020 Oct 11;6(10):e05190. Epub 2020 Oct 11.

Functional Neuroanatomy of Metabolism Regulation Laboratory, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Glucagon-like peptide-1 (GLP-1), whose agonists are widely prescribed, is a peptide proven effective in reducing obesity. Similarly, oxytocin (OXT) is a peptide known to increase satiety and help reduce body weight. In the present study, we aimed to examine the metabolic effects of co-administration of GLP-1 and OXT in diet-induced obesity (DIO) mice to elucidate their functions and interactions in the central nervous system. To this end, 40 DIO mice were subjected to stereotaxic surgery for the installation of an osmotic minipump and intracerebroventricular administration of GLP-1, OXT, or both. Initially, it was anticipated that co-administration of these anorexigenic peptides would be as effective as, if not more than, either GLP-1 or OXT alone in providing metabolic benefits to the obese mice. Interestingly, co-administration of OXT and GLP-1 offset the reductions in body weight and food intake promoted by either peptide alone. Co-administration also negated the decrease in fat and increase in lean mass produced by either peptide alone. Moreover, co-administration showed an equivalent calorimetric benefit as either peptide alone. Therefore, these results suggest antagonistic, rather than synergistic or additive, effects of centrally administered GLP-1 and OXT that attenuate the metabolic benefits of either peptide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2020.e05190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557924PMC
October 2020

Regulation of alternative macrophage activation by MSCs derived hypoxic conditioned medium, via the TGF-β1/Smad3 pathway.

BMB Rep 2020 Nov;53(11):600-604

Department of Biology Education, College of Education, Pusan National University, Busan 46241, Korea.

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-β1 expression, and TGF-β1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-β1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization. [BMB Reports 2020; 53(11): 600-604].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704222PMC
November 2020

Inhibitory effects of N-(acryloyl)benzamide derivatives on tyrosinase and melanogenesis.

Bioorg Med Chem 2019 09 19;27(17):3929-3937. Epub 2019 Jul 19.

Laboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University, Busan 46241, South Korea. Electronic address:

Targeting of tyrosinase has proven to be the best means of identifying safe, efficacious, and potent tyrosinase inhibitors for whitening skin. We designed and synthesized ten NAB (N-(acryloyl)benzamide) derivatives (1a-1j) using the Horner-Wadsworth-Emmons olefination of diethyl (2-benzamido-2-oxoethyl)phosphonate and appropriate benzaldehydes. A mushroom tyrosinase inhibitory assay showed compounds 1a (36.71 ± 2.14% inhibition) and 1j (25.99 ± 2.77% inhibition) inhibited tyrosinase more than the other eight NAB derivatives and kojic acid (21.56 ± 2.93% inhibition), and docking studies indicated 1a (-6.9 kcal/mole) and 1j (-7.5 kcal/mole) had stronger binding affinities for tyrosinase than kojic acid (-5.7 kcal/mole). At a concentration of 25 μM, 1a and 1j were nontoxic in B16F10 melanoma cells and exhibited stronger tyrosinase inhibition (59.70% and 76.77%, respectively) than kojic acid (50.30% inhibition) or arbutin (41.78% inhibition at 400 μM). Similarly, in B16F10 melanoma cells, compounds 1a and 1j at 25 μM decreased total melanin content by 47.97% and 61.77%, respectively (kojic acid; 38.98%). Similarities between inhibitions of tyrosinase activity and melanin contents suggested the anti-melanogenic effects of 1a and 1j were due to tyrosinase inhibition. The excellent DPPH scavenging activity of 1j suggests it might enhance in vivo effect on melanin contents. The study suggests compound 1j offers a potential starting point for the development of safe, potent tyrosinase inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2019.07.034DOI Listing
September 2019

Exosomes derived from microRNA-584 transfected mesenchymal stem cells: novel alternative therapeutic vehicles for cancer therapy.

BMB Rep 2018 Aug;51(8):406-411

Department of Biology Education, College of Education, Pusan National University, Busan 46241, Korea.

Exosomes are small membranous vesicles which contain abundant RNA molecules, and are transferred from releasing cells to uptaking cells. MicroRNA (miRNA) is one of the transferred molecules affecting the adopted cells, including glioma cells. We hypothesized that mesenchymal stem cells (MSCs) can secrete exosomes loading miRNA and have important effects on the progress of gliomas. To determine these effects by treating exosomal miRNA in culture media of miRNA mimic transfected MSCs, we assessed the in vitro cell proliferation and invasion capabilities, and the expression level of relative proteins associated with cell apoptosis, growth and migration. For animal studies, the mice injected with U87 cells were exposed to exosomes derived from miRNA-584-5p transfected MSCs, to confirm the influence of exosomal miRNA on the progress of glioma. Based on our results, we propose a new targeted cancer therapy wherein exosomes derived from miRNA transfected MSCs could be used to modulate tumor progress as the anticancer vehicles. [BMB Reports 2018; 51(8): 406-411].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130835PMC
http://dx.doi.org/10.5483/bmbrep.2018.51.8.105DOI Listing
August 2018

Tumor Inhibitory Effect of IRCR201, a Novel Cross-Reactive c-Met Antibody Targeting the PSI Domain.

Int J Mol Sci 2017 Sep 13;18(9). Epub 2017 Sep 13.

Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, Korea.

Hepatocyte growth factor receptor (HGFR, c-Met) is an essential member of the receptor tyrosine kinase (RTK) family that is often dysregulated during tumor progression, driving a malignant phenotypic state and modulating important cellular functions including tumor growth, invasion, metastasis, and angiogenesis, providing a strong rationale for targeting HGF/c-Met signaling axis in cancer therapy. Based on its protumorigenic potentials, we developed IRCR201, a potent antagonistic antibody targeting the plexin-semaphorin-integrin (PSI) domain of c-Met, using synthetic human antibody phage libraries. We characterized and evaluated the biochemical properties and tumor inhibitory effect of IRCR201 in vitro and in vivo. IRCR201 is a novel fully-human bivalent therapeutic antibody that exhibits cross-reactivity against both human and mouse c-Met proteins with high affinity and specificity. IRCR201 displayed low agonist activity and rapidly depleted total c-Met protein via the lysosomal degradation pathway, inhibiting c-Met-dependent downstream activation and attenuating cellular proliferation in various c-Met-expressing cancer cells. In vivo tumor xenograft models also demonstrated the superior tumor inhibitory responsiveness of IRCR201. Taken together, IRCR201 provides a promising therapeutic agent for c-Met-positive cancer patients through suppressing the c-Met signaling pathway and tumor growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms18091968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618617PMC
September 2017

GLP-1 Based Combination Therapy for Obesity and Diabetes.

J Obes Metab Syndr 2017 Sep 30;26(3):155-160. Epub 2017 Sep 30.

Functional Neuroanatomy of Metabolism Regulation Laboratory, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7570/jomes.2017.26.3.155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484915PMC
September 2017

The Korean Version of the Cognitive Assessment Scale for Stroke Patients (K-CASP): A Reliability and Validity Study.

Ann Rehabil Med 2017 Jun 29;41(3):362-375. Epub 2017 Jun 29.

Department of Rehabilitation Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Objective: To develop the Korean version of the Cognitive Assessment Scale for Stroke Patients (K-CASP) and to evaluate the test reliability and validity of the K-CASP in stroke patients.

Methods: The original CASP was translated into Korean, back-translated into English, then reviewed and compared with the original version. Thirty-three stroke patients were assessed independently by two examiners using the K-CASP twice, with a one-day interval, for a total of four test results. To evaluate the reliability of the K-CASP, intra-class correlation coefficients were used. Pearson correlations were calculated and simple regression analyses performed with the Korean version of Mini-Mental State Examination (K-MMSE) and the aphasia quotient (AQ) to assess the validity.

Results: The mean score was 24.42±9.47 (total score 36) for the K-CASP and 21.50±7.01 (total score 30) for the K-MMSE. The inter-rater correlation coefficients of the K-CASP were 0.992 on the first day and 0.995 on the second day. The intra-rater correlation coefficients of the K-CASP were 0.997 for examiner 1 and 0.996 for examiner 2. In the Pearson correlation analysis, the K-CASP score significantly correlated with the K-MMSE score (r=0.825, p<0.001). The coefficients of determination (r) of the AQ were 0.586 for the K-MMSE and 0.513 for the K-CASP in the simple regression analysis.

Conclusion: The K-CASP is a reliable and valid instrument for cognitive dysfunction screening in post-stroke patients. It is more applicable than other cognitive assessment tools in stroke patients with aphasia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5535/arm.2017.41.3.362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532341PMC
June 2017

Sonographic Findings of Polyneuropathy Associated With Cerebrotendinous Xanthomatosis: A Case Report.

Ann Rehabil Med 2017 Apr 27;41(2):313-317. Epub 2017 Apr 27.

Department of Rehabilitation Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Cerebrotendinous xanthomatosis is a rare autosomal recessive disease that involves multiple organs, including the peripheral nervous system. The present study is the first to report the ultrasonographic findings of peripheral nerves in a patient with cerebrotendinous xanthomatosis. The patient presented with bilateral Achilles tendon enlargement and foot hypesthesia. Sonographic examination revealed hypoechoic, swollen peripheral nerves with enlarged bilateral Achilles tendons. Since the ultrasonographic findings revealed peripheral involvement, the diagnosis of cerebrotendinous xanthomatosis was established after laboratory and genetic studies along with clinical findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5535/arm.2017.41.2.313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426266PMC
April 2017

Prescription patterns for patients with schizophrenia in Korea: a focus on antipsychotic polypharmacy.

Clin Psychopharmacol Neurosci 2014 Aug 12;12(2):128-36. Epub 2014 Aug 12.

Department of Psychiatry, Inha University Hospital, Incheon, Korea.

Objective: This study investigated the prescription patterns for Korean patients with schizophrenia with a particular focus on antipsychotic polypharmacy. All data were gathered from patients presenting at 41 tertiary university hospitals and 8 secondary hospitals.

Methods: Data from three multicenter studies conducted in Korea were retrospectively reviewed and integrated to identify patients with schizophrenia who had their antipsychotic medication switched to paliperidone extended-release between 2008 and 2009. The rates for antipsychotic polypharmacy, combined use of different antipsychotic classes with a special focus on atypical antipsychotics, and psychotropic polypharmacy using benzodiazepines, mood stabilizers, and other relevant drugs were identified.

Results: Of the 851 Korean patients analyzed in this study, 20.4% (n=173) had been prescribed antipsychotic polypharmacy. Of the 678 patients receiving antipsychotic monotherapy, 6.9% (n=47) were prescribed a typical antipsychotic and 93.1% (n=631) were prescribed an atypical antipsychotic. Of the 173 patients receiving a combination of antipsychotic drugs, only 6.4% (n=11) had been prescribed polypharmacy with typical antipsychotics, while 46.82% (n=81) were prescribed atypical+atypical antipsychotics or typical+atypical antipsychotics. The highest co-prescription rates for other psychotropic drugs in conjunction with antipsychotics included benzodiazepines (30.3%), anticholinergic drugs (28.8%), antidepressants (13.3%), β-blockers (10.1%), and mood stabilizers (8.7%).

Conclusion: The present findings demonstrate that the rate of antipsychotic polypharmacy is relatively low in Korea and that Korean clinicians prefer to prescribe atypical, rather than typical, antipsychotic drugs. This suggests that there is a distinct prescription pattern in Korea that is focused on antipsychotic polypharmacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.9758/cpn.2014.12.2.128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153859PMC
August 2014

MHY884, a newly synthesized tyrosinase inhibitor, suppresses UVB-induced activation of NF-κB signaling pathway through the downregulation of oxidative stress.

Bioorg Med Chem Lett 2014 Mar 25;24(5):1344-8. Epub 2014 Jan 25.

Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea. Electronic address:

The skin is the primary target of prolonged and repeated ultraviolet (UVB) irradiation which induces cutaneous inflammation and pigmentation. Nuclear factor κB (NF-κB) is the major factor mediating UVB-induced inflammatory responses through the expression of various proinflammatory proteins such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). We have previously reported that the synthetic novel compound 4-(5-chloro-2,3-dihydrobenzo[d]thiazol-2-yl)-2,6-dimethoxyphenol (MHY884) strongly suppressed tyrosinase activity and melanin synthesis in B16F10 melanoma cells. In the present study, we investigated the effect of MHY884 on the inhibition of UVB-induced NF-κB activation and its proinflammatory downstream proteins through the suppression of oxidative stress in an in vivo model of photoaging. Generation of reactive oxygen species (ROS) and peroxynitrite was measured in vitro and in B16F10 melanoma cells to verify the scavenging activity of MHY884. MHY884 suppressed oxidative stress both in vitro and in the melanoma cells in a dose-dependent manner. Next, melanin-possessing hairless mice were pre-treated with MHY884 and then irradiated with UVB repeatedly. Topical application of MHY884 attenuated UVB-induced oxidative stress, resulting in reduced NF-κB activity. Pre-treatment with MHY884 inhibited Akt and IκB kinase α/β signaling pathways, leading to decreased translocation and phosphorylation of p65, a subunit of NF-κB. This result correlated with the expression levels of iNOS and COX-2 in the skin of MHY884-treated mice. Thus, the novel tyrosinase inhibitor MHY884 suppressed NF-κB activation signaling pathway by scavenging UVB-induced oxidative stress. The discovery of MHY884, a novel tyrosinase inhibitor that targets NF-κB signaling, is significant, because this compound is a promising protective agent against UVB-induced skin damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2014.01.040DOI Listing
March 2014

The Influence of Previous Antipsychotic Polypharmacy Versus Monotherapy on the Effectiveness of Antipsychotic after Switching to Paliperidone Extended-release.

Clin Psychopharmacol Neurosci 2013 Dec 24;11(3):152-7. Epub 2013 Dec 24.

Department of Psychiatry, Inha University Hospital, Incheon, Korea.

Objective: Although antipsychotic polypharmacy is widely used in the pharmacotherapy of schizophrenia, its effectiveness is controversial. In particular, clinicians tend to avoid switching to monotherapy in patients who have been prescribed polypharmacy. In the present study, the authors investigate whether there is difference in time to discontinuation of antipsychotics between patients on previous monotherapy or polypharmacy.

Methods: Pooled analysis was conducted on two 24-week, multicenter, open-label, non-comparative studies that were originally designed to investigate the effectiveness of switching to paliperidone extended-release (ER) in patients with schizophrenia. Patients were divided into two groups according to previously prescribed antipsychotics, that is, to a polypharmacy group or a monotherapy group. The primary outcome measure was time to discontinuation of paliperidone ER. In addition, the authors sought to identify clinical variables that influence time to discontinuation.

Results: Before switching to paliperidone ER, 535 of 673 (79.5%) patients were prescribed antipsychotic monotherapy, and the remaining 138 (20.5%) patients were prescribed antipsychotic polypharmacy. No significant differences in time to discontinuation of paliperidone ER were observed between the polypharmacy and monotherapy groups. Personal and social performance scale score was the only factor found to influence time to discontinuation of paliperidone ER. No differences in psychopathology or adverse effects were found between the monotherapy and polypharmacy groups.

Conclusion: Our results suggest that number of antipsychotics prescribed before switching to monotherapy does not influence clinical prognosis in patients with schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.9758/cpn.2013.11.3.152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897764PMC
December 2013