Publications by authors named "Sang Hun Lee"

559 Publications

Development of a patient-report pressure algometer for the quantification of abdominal examination.

Integr Med Res 2021 Dec 24;10(4):100742. Epub 2021 May 24.

College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

Background: Abdominal examination (AE), one of the primary diagnostic tools used in traditional Korean medicine (TKM), has a limitation of being subjective due to depending on individual practitioner's experience. Therefore, we devised a novel patient-report pressure algometer (PA) and performed a clinical trial to investigate its validity.

Methods: In total, 44 participants with functional dyspepsia and 44 healthy participants completed the study. The participants were allocated into one of two groups according to the existence of abdominal stiffness at 5 acupoints or abdominal tenderness at 12 acupoints diagnosed by TKM doctors. The pressure depth and pressure pain threshold (PPT) were evaluated using the PA at the same acupoints. We assessed the validity (sensitivity and specificity) of PA and calculated the area under the curve (AUC) and optimal cutoff value of the test variables (pressure depth and PPT) to criterion standards (abdominal stiffness and tenderness).

Results: Pressure depth and PPT assessed by PA showed high sensitivity and specificity in diagnosing abdominal stiffness and tenderness. The validity at CV-14 of diagnosing abdominal tenderness with PPT by PA had a sensitivity of 73.1%, specificity of 77.8%, and an AUC of 0.807 with a value of < 0.001.

Conclusion: This study may provide evidence of standardization and quantification of AE through PA.
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http://dx.doi.org/10.1016/j.imr.2021.100742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185239PMC
December 2021

Water condition in biotrickling filtration for the efficient removal of gaseous contaminants.

Crit Rev Biotechnol 2021 Jun 9:1-18. Epub 2021 Jun 9.

Department of Occupational and Environmental Health, School of Public Health, Lanzhou University, Lanzhou, P. R. China.

Biofiltration (BF) facilitates the removal of organic and inorganic compounds through microbial reactions. Water is one of the most important elements in biotrickling filters that provides moisture and nutrients to microbial biofilms. The maintenance of proper trickle watering is very critical in biotrickling filtration because the flow rate of the trickling water significantly influences contaminant removal, and its optimal control is associated with various physicochemical and biological mechanisms. The lack of water leads to the drying of the media, creating several issues, including the restricted absorption of hydrophilic contaminants and the inhibition of microbial activities, which ultimately deteriorates the overall contaminant removal efficiency (RE). Conversely, an excess of water limits the mass transfer of oxygen or hydrophobic gases. In-depth analysis is required to elucidate the role of trickle water in the overall performance of biotrickling filters. The processes involved in the treatment of various polluted gases under specific water conditions have been summarized in this study. Recent microscopic studies on biofilms were reviewed to explain the process by which water stress influences the biological mechanisms involved in the treatment of hydrophobic contaminated gases. In order to maintain an effective mass transfer, hydrodynamic and biofilm conditions, a coherent understanding of water stress and the development of extracellular polymeric substances (EPS) in biofilms is necessary. Future studies on the realistic local distribution of hydrodynamic patterns (trickle flow, water film thickness, and wet efficiency), integrated with biofilm distributions, should be conducted with respect to EPS development.
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http://dx.doi.org/10.1080/07388551.2021.1917506DOI Listing
June 2021

Nanoscale Terahertz Monitoring on Multiphase Dynamic Assembly of Nanoparticles under Aqueous Environment.

Adv Sci (Weinh) 2021 06 24;8(11):e2004826. Epub 2021 Mar 24.

Sensor System Research Centre, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.

Probing the kinetic evolution of nanoparticle (NP) growth in liquids is essential for understanding complex nano-phases and their corresponding functions. Terahertz (THz) sensing, an emerging technology for next-generation laser photonics, has been developed with unique photonic features, including label-free, non-destructive, and molecular-specific spectral characteristics. Recently, metasurface-based sensing platforms have helped trace biomolecules by overcoming low THz absorption cross-sectional limits. However, the direct probing of THz signals in aqueous environments remains difficult. Here, the authors report that vertically aligned nanogap-hybridized metasurfaces can efficiently trap traveling NPs in the sensing region, thus enabling us to monitor the real-time kinetic evolution of NP assemblies in liquids. The THz photonics approach, together with an electric tweezing technique via spatially matching optical hotspots to particle trapping sites with a nanoscale spatial resolution, is highly promising for underwater THz analysis, forging a route toward unraveling the physicochemical events of nature within an ultra-broadband wavelength regime.
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http://dx.doi.org/10.1002/advs.202004826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188200PMC
June 2021

Recent Advances in Surface-Enhanced Raman Scattering Magnetic Plasmonic Particles for Bioapplications.

Nanomaterials (Basel) 2021 May 4;11(5). Epub 2021 May 4.

Department of Bioscience and Biotechnology, Konkuk University,120 Neungdong-ro, Gwangjin-Gu, Seoul 05029, Korea.

The surface-enhanced Raman scattering (SERS) technique, that uses magnetic plasmonic particles (MPPs), is an advanced SERS detection platform owing to the synergetic effects of the particles' magnetic and plasmonic properties. As well as being an ultrasensitive and reliable SERS material, MPPs perform various functions, such as aiding in separation, drug delivery, and acting as a therapeutic material. This literature discusses the structure and multifunctionality of MPPs, which has enabled the novel application of MPPs to various biological fields.
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http://dx.doi.org/10.3390/nano11051215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147842PMC
May 2021

Neural stem cells derived from human midbrain organoids as a stable source for treating Parkinson's disease: Midbrain organoid-NSCs (Og-NSC) as a stable source for PD treatment.

Prog Neurobiol 2021 May 28:102086. Epub 2021 May 28.

Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Hanyang Biomedical Research Institute, Hanyang University, Seoul, Republic of Korea; Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea. Electronic address:

Successful clinical translation of stem cell-based therapy largely relies on the scalable and reproducible preparation of donor cells with potent therapeutic capacities. In this study, midbrain organoids were yielded from human pluripotent stem cells (hPSCs) to prepare cells for Parkinson's disease (PD) therapy. Neural stem/precursor cells (NSCs) isolated from midbrain organoids (Og-NSCs) expanded stably and differentiated into midbrain-type dopamine(mDA) neurons, and an unprecedentedly high proportion expressed midbrain-specific factors, with relatively low cell line and batch-to-batch variations. Single cell transcriptome analysis followed by in vitro assays indicated that the majority of cells in the Og-NSC cultures are ventral midbrain (VM)-patterned with low levels of cellular senescence/aging and mitochondrial stress, compared to those derived from 2D-culture environments. Notably, in contrast to current methods yielding mDA neurons without astrocyte differentiation, mDA neurons that differentiated from Og-NSCs were interspersed with astrocytes as in the physiologic brain environment. Thus, the Og-NSC-derived mDA neurons exhibited improved synaptic maturity, functionality, resistance to toxic insults, and faithful expressions of the midbrain-specific factors, in vitro and in vivo long after transplantation. Consequently, Og-NSC transplantation yielded potent therapeutic outcomes that are reproducible in PD model animals. Collectively, our observations demonstrate that the organoid-based method may satisfy the demands needed in the clinical setting of PD cell therapy.
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http://dx.doi.org/10.1016/j.pneurobio.2021.102086DOI Listing
May 2021

Inactivation of Presenilin in inhibitory neurons results in decreased GABAergic responses and enhanced synaptic plasticity.

Mol Brain 2021 May 25;14(1):85. Epub 2021 May 25.

Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

Mutations in the Presenilin genes are the major genetic cause of Alzheimer's disease (AD). Presenilin (PS) is highly expressed in the hippocampus, which is particularly vulnerable in AD. Previous studies of PS function in the hippocampus, however, focused exclusively on excitatory neurons. Whether PS regulates inhibitory neuronal function remained unknown. In the current study, we investigate PS function in GABAergic neurons by performing whole-cell and field-potential electrophysiological recordings using acute hippocampal slices from inhibitory neuron-specific PS conditional double knockout (IN-PS cDKO) mice at 2 months of age, before the onset of age-dependent loss of interneurons. We found that the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) is reduced in hippocampal CA1 neurons of IN-PS cDKO mice, whereas the amplitude of sIPSCs is normal. Moreover, the efficacy of inhibitory neurotransmission as assessed with synaptic input/output relations for evoked mono- and di-synaptic IPSCs is markedly lowered in hippocampal CA1 neurons of IN-PS cDKO mice. Consistent with these findings, IN-PS cDKO mice display enhanced paired-pulse facilitation, frequency facilitation and long-term potentiation in the Schaffer collateral-CA1 pathway. Interestingly, depletion of intracellular Ca stores by inhibition of sarcoendoplasmic reticulum Ca ATPase results in a reduction of IPSC amplitude in control hippocampal neurons but not in IN-PS cDKO neurons, suggesting that impaired intracellular calcium homeostasis in the absence of PS may contribute to the deficiencies in inhibitory neurotransmission. Furthermore, the amplitude of IPSCs induced by short trains of presynaptic stimulation and paired-pulse ratio are decreased in IN-PS cDKO mice. These findings show that inactivation of PS in interneurons results in decreased GABAergic responses and enhanced synaptic plasticity in the hippocampus, providing additional evidence for the importance of PS in the regulation of synaptic plasticity and calcium homeostasis.
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http://dx.doi.org/10.1186/s13041-021-00796-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152317PMC
May 2021

Free-floating and spinning thrombus of the basilar artery: A case report.

Medicine (Baltimore) 2021 May;100(21):e25696

Department of Neurology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of Korea.

Rationale: Free-floating thrombi in the intracranial artery are rare. We report a case of a free-floating and spinning thrombus caused by turbulent flow distal to the basilar artery stenosis. We compare thrombus changes in a series of images according to time and describe the approach to treatment and thrombosis resolution..

Patient Concerns: A 55-year-old man presented to the emergency department on March 21, 2020, with left-sided weakness, bilateral limb ataxia, and a one-day history of dysarthria. Brain magnetic resonance imaging showed multifocal infarctions in the pons and cerebellum with severe basilar stenosis.

Diagnoses: Digital subtraction angiography showed severe focal stenosis. A relatively large oval-shaped mobile thrombus was observed spinning due to turbulent flow at the distal portion of the stenosis.

Interventions: We administered a combination antithrombotic regimen of warfarin and clopidogrel for 50 days.

Outcomes: No thrombus was observed on the third follow-up digital subtraction angiography.

Lessons: No previous study has directly observed a mobile thrombus in the intracranial artery using digital subtraction angiography. We used a combination antithrombotic strategy, which was effective after long-term, rather than short-term, use.
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http://dx.doi.org/10.1097/MD.0000000000025696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154379PMC
May 2021

Preparedness of personal protective equipment and implementation of new CPR strategies for patients with out-of-hospital cardiac arrest in the COVID-19 era.

Resusc Plus 2020 Sep 25;3:100015. Epub 2020 Jun 25.

Department of Emergency Medicine, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea.

Background: In February and March 2020, healthcare providers and citizens in Daegu, South Korea, experienced the onslaught of a large-scale community epidemic of COVID-19. This had a profound impact on patients who experienced out-of-hospital cardiac arrest (OHCA).

Methods: We conducted a retrospective observational study of 171 OHCA patients based on the multicenter WinCOVID registry. Demographic and clinical characteristics, overall survival, COVID-19 related data, as well as personal protective equipment (PPE) and resuscitation techniques used during the COVID-19 outbreak were evaluated and compared with outcomes from a 2018 historical cohort (n ​= ​158).

Results: Among the interventions, high-level PPE was introduced and standard cardiopulmonary resuscitation was changed to chest compressions using mechanical devices. All OHCA patients were treated as confirmed or suspicious for COVID-19 regardless of symptoms. Furthermore, complete or partial closures of emergency centers and the number of medical personnel requiring self-isolation decreased in response to the introduction of isolated resuscitation units. However, the adjusted odds ratio and 95% confidence intervals for survival discharge and favorable neurologic outcome were 0.51 (0.25-0.97) and 0.45 (0.21-1.07) compared with those in the 2018 historical cohort.

Conclusions: Responses to the COVID-19 pandemic included changes to current PPE strategies and introduction of isolated resuscitation units; the latter intervention reduced the number of unexpected closures and quarantines of emergency resources early on during the COVID-19 outbreak. Given the possibility of future outbreaks, we need to have revised resuscitation strategies and the capacity to commandeer emergency resources for OHCA patients.
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http://dx.doi.org/10.1016/j.resplu.2020.100015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315986PMC
September 2020

Prion Protein of Extracellular Vesicle Regulates the Progression of Colorectal Cancer.

Cancers (Basel) 2021 Apr 29;13(9). Epub 2021 Apr 29.

Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Korea.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death due to its aggressive metastasis in later stages. Although there is a growing interest in the tumorigenic role of cellular prion protein (PrP) in the process of metastasis, the precise mechanism behind the cellular communication involving prion proteins remains poorly understood. This study found that hypoxic tumor microenvironment increased the PrP-expressing exosomes from CRC, and these exosomes regulate the CRC cell behavior and tumor progression depending on the expression of PrP. Hypoxic exosomes from CRC cells promoted sphere formation, the expression of tumor-inducing genes, migration, invasion, and tumor growth. Furthermore, these exosomes increased endothelial permeability, migration, invasion, and angiogenic cytokine secretion. These effects were associated with PrP expression. Application of anti-PrP antibody with 5-fluorouracil significantly suppressed the CRC progression in a murine xenograft model. Taken together, these findings indicate that PrP-expressing exosomes secreted by hypoxic CRC cells are a key factor in the tumorigenic CRC-to-CRC and CRC-to-endothelial cell communication. Significance: These findings suggest that inhibiting PrP in hypoxic exosomes during chemotherapy may be an effective therapeutic strategy in colorectal cancer.
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http://dx.doi.org/10.3390/cancers13092144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124505PMC
April 2021

Glucose Detection of 4-Mercaptophenylboronic Acid-Immobilized Gold-Silver Core-Shell Assembled Silica Nanostructure by Surface Enhanced Raman Scattering.

Nanomaterials (Basel) 2021 Apr 8;11(4). Epub 2021 Apr 8.

Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea.

The importance of glucose in many biological processes continues to garner increasing research interest in the design and development of efficient biotechnology for the sensitive and selective monitoring of glucose. Here we report on a surface-enhanced Raman scattering (SERS) detection of 4-mercaptophenyl boronic acid (4-MPBA)-immobilized gold-silver core-shell assembled silica nanostructure ([email protected]@[email protected]) for quantitative, selective detection of glucose in physiologically relevant concentration. This work confirmed that 4-MPBA converted to 4-mercaptophenol (4-MPhOH) in the presence of HO. In addition, a calibration curve for HO detection of 0.3 µg/mL was successfully detected in the range of 1.0 to 1000 µg/mL. Moreover, the [email protected]@[email protected] for glucose detection was developed in the presence of glucose oxidase (GOx) at the optimized condition of 100 µg/mL GOx with 1-h incubation time using 20 µg/mL [email protected]@[email protected] and measuring Raman signal at 67 µg/mL [email protected]@Ag. At the optimized condition, the calibration curve in the range of 0.5 to 8.0 mM was successfully developed with an LOD of 0.15 mM. Based on those strategies, the SERS detection of glucose can be achieved in the physiologically relevant concentration range and opened a great promise to develop a SERS-based biosensor for a variety of biomedicine applications.
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http://dx.doi.org/10.3390/nano11040948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068217PMC
April 2021

Vulnerability of cholecystokinin-expressing GABAergic interneurons in the unilateral intrahippocampal kainate mouse model of temporal lobe epilepsy.

Exp Neurol 2021 Aug 26;342:113724. Epub 2021 Apr 26.

Department of Neuroscience, University of Kentucky, Lexington, KY 40536, USA; Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address:

Temporal lobe epilepsy (TLE) is characterized by recurrent spontaneous seizures and behavioral comorbidities. Reduced hippocampal theta oscillations and hyperexcitability that contribute to cognitive deficits and spontaneous seizures are present beyond the sclerotic hippocampus in TLE. However, the mechanisms underlying compromised network oscillations and hyperexcitability observed in circuits remote from the sclerotic hippocampus are largely unknown. Cholecystokinin (CCK)-expressing basket cells (CCKBCs) critically participate in hippocampal theta rhythmogenesis, and regulate neuronal excitability. Thus, we examined whether CCKBCs were vulnerable in nonsclerotic regions of the ventral hippocampus remote from dorsal sclerotic hippocampus using the intrahippocampal kainate (IHK) mouse model of TLE, targeting unilateral dorsal hippocampus. We found a decrease in the number of CCK+ interneurons in ipsilateral ventral CA1 regions from epileptic mice compared to those from sham controls. We also found that the number of boutons from CCK+ interneurons was reduced in the stratum pyramidale, but not in other CA1 layers, of ipsilateral hippocampus in epileptic mice, suggesting that CCKBCs are vulnerable. Electrical recordings showed that synaptic connectivity and strength from surviving CCKBCs to CA1 pyramidal cells (PCs) were similar between epileptic mice and sham controls. In agreement with reduced CCKBC number in TLE, electrical recordings revealed a significant reduction in amplitude and frequency of IPSCs in CA1 PCs evoked by carbachol (commonly used to excite CCK+ interneurons) in ventral CA1 regions from epileptic mice versus sham controls. These findings suggest that loss of CCKBCs beyond the hippocampal lesion may contribute to hyperexcitability and compromised network oscillations in TLE.
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http://dx.doi.org/10.1016/j.expneurol.2021.113724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192495PMC
August 2021

Enhanced inhibition of tumor growth using TRAIL-overexpressing adipose-derived stem cells in combination with the chemotherapeutic agent CPT-11 in castration-resistant prostate cancer.

Prostate Int 2021 Mar 31;9(1):31-41. Epub 2020 Jul 31.

Department of Urology, Soonchunhyang University School of Medicine, Seoul, Korea.

Background: This study investigated the inhibition of tumor growth in castrate-resistant prostate cancer (CRPC)-bearing mice by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-overexpressing adipose-derived stem cells (ADSCs) (hTERT-ADSC.sTRAIL), which was enhanced by combined treatment with CPT-11.

Materials And Methods: An hTERT-ADSC.sTRAIL cell line was established by transfection with a lentiviral vector (CLV-Ubic) encoding the human sTRAIL gene. Quantitative polymerase chain reaction and Western blots were performed to confirm gene overexpression. An invasion study for the selective migration ability toward PC3 cells was performed. In the study, the tumor volume in mice treated with ADSC. sTRAIL and CPT-11 was measured.

Results: Carboxylesterase was generated from hTERT-ADSCs. The gene expression of sTRAIL from hTERT-ADSC.sTRAIL was shown. The directional migration of ADSC.sTRAIL cells toward PC3 cells was significantly stimulated by PC3 cells ( < 0.05). In the study, the viability of PC3 cells significantly decreased in the presence of ADSC.sTRAIL (62.7 ± 2.0%) and CPT-11 compared with that of CPT-11 alone (83.0 ± 1.0%) at a cell ratio as low as 0.05 (PC3: ADSC.sTRAIL) ( < 0.05). The proportion of apoptotic PC3 cells significantly increased in the presence of ADSC.sTRAIL (37.2 ± 2.1%) and CPT-11 compared with that of CPT-11 alone (16.5 ± 1.0%) ( < 0.05). In the study, the inhibition of tumor growth in CRPC-bearing mice by TRAIL-overexpressing adipose stem cells was enhanced by combined treatment with the chemotherapeutic agent CPT-11 compared with that in the treatment with cpt-11 alone. Immunohistochemical staining of the removed tumors showed anti-TRAIL-positive cells and apoptotic bodies after hTERT-ADSC.sTRAIL treatment or combined treatment with hTERT-ADSC.sTRAIL and CPT-11.

Conclusions: Therapeutic stem cells expressing sTRAIL genes combined with CPT-11 can provide a new strategy for treating CRPC in clinical trials using the patients' own ADSCs.
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http://dx.doi.org/10.1016/j.prnil.2020.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053698PMC
March 2021

Delays in the Management of Patients with Acute Ischemic Stroke during the COVID-19 Outbreak Period: A Multicenter Study in Daegu, Korea.

Emerg Med Int 2021 20;2021:6687765. Epub 2021 Mar 20.

Department of Neurology, Dongsan Medical Center, Keimyung University, Daegu 42601, Republic of Korea.

Background: Timely treatment is important for patients with acute ischemic stroke (AIS). However, the coronavirus disease 2019 (COVID-19) outbreak may have caused delays in patient management. Therefore, we analyzed the prognosis and the time spent at the prehospital and hospital stages in managing patients diagnosed with AIS during the COVID-19 outbreak.

Methods: This retrospective study evaluated patients diagnosed with AIS in the emergency department (ED) at five medical centers in Daegu city between February 18 and April 17 each year from 2018 to 2020. Data on the patients' clinical features and time spent on management were collected and compared according to COVID-19 and pre-COVID-19 summaries.

Results: From a total of 533 patients diagnosed with AIS, 399 patients visited the ED before COVID-19 and 134 during the COVID-19 outbreak. During the COVID-19 outbreak, compared with pre-COVID-19, AIS patients had poor National Institute of Health Stroke Scale scores at the initial hospital visit (6 vs. 4, =0.013) and discharge (3 vs. 2, =0.001). During the COVID-19 outbreak, the proportion of direct visits to hospitals through public emergency medical services (EMS) increased, and the onset of symptoms-to-ED door time via the public EMS was delayed (87 min vs. 68 min, =0.006).

Conclusions: The prognosis of AIS patients during the COVID-19 outbreak was worse than that of pre-COVID-19 patients with delays at the prehospital stage, despite the need for timely care.
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http://dx.doi.org/10.1155/2021/6687765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988744PMC
March 2021

Synthesis of Densely Immobilized Gold-Assembled Silica Nanostructures.

Int J Mol Sci 2021 Mar 3;22(5). Epub 2021 Mar 3.

Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea.

In this study, dense gold-assembled SiO nanostructure ([email protected]) was successfully developed using the Au seed-mediated growth. First, SiO (150 nm) was prepared, modified by amino groups, and incubated by gold nanoparticles (ca. 3 nm Au metal nanoparticles (NPs)) to immobilize Au NPs to SiO surface. Then, Au NPs were grown on the prepared [email protected] seed by reducing chloroauric acid (HAuCl by ascorbic acid (AA) in the presence of polyvinylpyrrolidone (PVP). The presence of bigger (ca. 20 nm) Au NPs on the SiO surface was confirmed by transmittance electronic microscopy (TEM) images, color changes to dark blue, and UV-vis spectra broadening in the range of 450 to 750 nm. The [email protected] nanostructure showed several advantages compared to the hydrofluoric acid (HF)-treated [email protected], such as easy separation, surface modification stability by 11-mercaptopundecanoic acid (R-COOH), 11-mercapto-1-undecanol (R-OH), and 1-undecanethiol (R-CH), and a better peroxidase-like catalysis activity for 5,5'-Tetramethylbenzidine (TMB) and hydrogen peroxide (HO) reaction. The catalytic activity of [email protected] was two times better than that of HF-treated [email protected] When [email protected] nanostructure was used as a surface enhanced Raman scattering (SERS) substrate, the signal of 4-aminophenol (4-ATP) on the surface of [email protected] was also stronger than that of HF-treated [email protected] This study provides a potential method for nanoparticle preparation which can be replaced for Au NPs in further research and development.
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http://dx.doi.org/10.3390/ijms22052543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961356PMC
March 2021

Impaired pattern separation in Tg2576 mice is associated with hyperexcitable dentate gyrus caused by Kv4.1 downregulation.

Mol Brain 2021 03 30;14(1):62. Epub 2021 Mar 30.

Department of Physiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes memory loss. Most AD researches have focused on neurodegeneration mechanisms. Considering that neurodegenerative changes are not reversible, understanding early functional changes before neurodegeneration is critical to develop new strategies for early detection and treatment of AD. We found that Tg2576 mice exhibited impaired pattern separation at the early preclinical stage. Based on previous studies suggesting a critical role of dentate gyrus (DG) in pattern separation, we investigated functional changes in DG of Tg2576 mice. We found that granule cells in DG (DG-GCs) in Tg2576 mice showed increased action potential firing in response to long depolarizations and reduced 4-AP sensitive K-currents compared to DG-GCs in wild-type (WT) mice. Among Kv4 family channels, Kv4.1 mRNA expression in DG was significantly lower in Tg2576 mice. We confirmed that Kv4.1 protein expression was reduced in Tg2576, and this reduction was restored by antioxidant treatment. Hyperexcitable DG and impaired pattern separation in Tg2576 mice were also recovered by antioxidant treatment. These results highlight the hyperexcitability of DG-GCs as a pathophysiologic mechanism underlying early cognitive deficits in AD and Kv4.1 as a new target for AD pathogenesis in relation to increased oxidative stress.
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http://dx.doi.org/10.1186/s13041-021-00774-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011083PMC
March 2021

Conclusion and Perspective.

Adv Exp Med Biol 2021 ;1309:289-292

Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.

Nanotechnology is a rapidly growing area of development by numerous research groups across the world with its potential applications gaining recognition since the 1950s across various fields. During the last decade of the twentieth century, researchers have actively engaged in the synthesis of nanoparticles and investigation of their physicochemical properties. Advancing the research momentum forward at the beginning of the twenty-first century, rapid development of nanoscience allowed to demonstrate unprecedented advantages of the nanomaterials and its applications in a wide range of fields. The interdisciplinary nature of nanoscience and its expansion has led to establishment of new laboratories and research centers, with increasing needs on training and educating young scientists in advanced laboratory protocols. In addition, pedagogical demands in nanotechnology and nanomaterials have resulted an emergence of new dedicated curriculums at universities which has sped up the development of nanoscience and its contribution to the body of knowledge in natural science.
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http://dx.doi.org/10.1007/978-981-33-6158-4_13DOI Listing
March 2021

Optical and Electron Microscopy for Analysis of Nanomaterials.

Adv Exp Med Biol 2021 ;1309:277-287

Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.

Not only is fabrication important for research in materials science, but also materials characterization and analysis. Special microscopes capable of ultra-high magnification are more essential for observing and analyzing nanoparticles than for macro-size particles. Recently, electron microscopy (EM) and scanning probe microscopy (SPM) are commonly used for observing and analyzing nanoparticles. In this chapter, the basic principles of various techniques in optical and electron microscopy are described and classified. In particular, techniques such as transmission electron microscopy (TEM) and scanning electron microscopy (SEM) are explained.
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http://dx.doi.org/10.1007/978-981-33-6158-4_12DOI Listing
March 2021

Carbon Nanomaterials for Biomedical Application.

Adv Exp Med Biol 2021 ;1309:257-276

Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.

The use of carbon-based nanomaterials (CNs) with outstanding properties has been rising in many scientific and industrial application fields. These CNs represent a tunable alternative for applications with biomolecules, which allow interactions in either covalent or noncovalent way. Diverse carbon-derived nanomaterial family exhibits unique features and has been widely exploited in various biomedical applications, including biosensing, diagnosis, cancer therapy, drug delivery, and tissue engineering. In this chapter, we aim to present an overview of CNs with a particular interest in intrinsic structural, electronic, and chemical properties. In particular, the detailed properties and features of CNs and its derivatives, including carbon nanotube (CNT), graphene, graphene oxide (GO), and reduced GO (rGO) are summarized. The interesting biomedical applications are also reviewed in order to offer an overview of the possible fields for scientific and industrial applications of CNs.
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http://dx.doi.org/10.1007/978-981-33-6158-4_11DOI Listing
March 2021

Bioapplications of Nanomaterials.

Adv Exp Med Biol 2021 ;1309:235-255

Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.

Nanobiotechnology is known as the application of nanoscaled techniques in biology which bridges natural science to living organism for improving the quality of life of humans. Nanotechnology was first issued in 1959 and has been rapidly developed, supplying numerous benefits to basic scientific academy and to clinical application including human healthcare, specifically in cancer therapy. This chapter discusses recent advances and potentials of nanotechnology in pharmaceutics, therapeutics, biosensing, bioimaging, and gene delivery that demonstrate the multifunctionality of nanotechnology.
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http://dx.doi.org/10.1007/978-981-33-6158-4_10DOI Listing
March 2021

Lithography Technology for Micro- and Nanofabrication.

Adv Exp Med Biol 2021 ;1309:217-233

Department of Bionano Engineering, Hanyang University, Ansan, South Korea.

Micro and nanofabrication technologies are integral to the development of miniaturized systems. Lithography plays a key role in micro and nanofabrication techniques. Since high functional miniaturized systems are required in various fields, such as the development of a semiconductor, chemical and biological analysis, and biomedical researches, lithography techniques have been developed and applied for their appropriate purpose. Lithography can be classified into conventional and unconventional lithography, or top-down and bottom-up, or with mask and mask-less approaches. In this chapter, various lithography techniques are categorized and classified into conventional and unconventional lithography. In the first part, photolithography, electron beam, and focused-ion beam lithography are introduced as conventional lithography techniques. The second part introduces nanoimprint lithography, deformation lithography, and colloidal lithography as unconventional lithography techniques. In the last part, the pros and cons of each lithography are discussed for an appropriate design of fabrication processes.
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http://dx.doi.org/10.1007/978-981-33-6158-4_9DOI Listing
March 2021

Magnetic Nanoparticles.

Adv Exp Med Biol 2021 ;1309:191-215

Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.

Magnetic nanoparticles have been used in various fields such as data storage, biomedicine, or bioimaging with their unique magnetic property. With their low toxicity, the importance of magnetic nanoparticles keeps increasing especially in biological field. In this chapter, content suitable for scientific inquirers or undergraduates to acquire basic knowledge about nanotechnology is introduced and then recent research trends in nanotechnology are covered.
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http://dx.doi.org/10.1007/978-981-33-6158-4_8DOI Listing
March 2021

Plasmonic Nanoparticles: Advanced Researches (II).

Adv Exp Med Biol 2021 ;1309:161-190

Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.

Following the previous chapter, recent synthetic methods of metal-based nanoparticles and their applications based on plasmonic resonance properties are described in this chapter. This differs from the previous chapter, which described the general uses of metal-based nanoparticles, in that various recent advanced applications of metal-based nanoparticles are described in this chapter.
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http://dx.doi.org/10.1007/978-981-33-6158-4_7DOI Listing
March 2021

Plasmonic Nanoparticles: Basics to Applications (I).

Adv Exp Med Biol 2021 ;1309:133-159

Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.

This review presents the main characteristics of metal nanoparticles (NPs), especially consisting of noble metal such as Au and Ag, and brief information on their synthesis methods. The physical and chemical properties of the metal NPs are described, with a particular focus on the optically variable properties (surface plasmon resonance based properties) and surface-enhanced Raman scattering of plasmonic materials. In addition, this chapter covers ways to achieve advances by utilizing their properties in the biological studies and medical fields (such as imaging, diagnostics, and therapeutics). These descriptions will help researchers new to nanomaterials for biomedical diagnosis to understand easily the related knowledge and also will help researchers involved in the biomedical field to learn about the latest research trends.
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http://dx.doi.org/10.1007/978-981-33-6158-4_6DOI Listing
March 2021

Luminescent Nanomaterials (II).

Adv Exp Med Biol 2021 ;1309:97-132

Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.

In this review, we focus on sensing techniques and biological applications of various luminescent nanoparticles including quantum dot (QD), up-conversion nanoparticles (UCNPs) following the previous chapter. Fluorescent phenomena can be regulated or shifted by interaction between biological targets and luminescence probes depending on their distance, which is so-called Fӧrster resonance energy transfer (FRET). QD-based FRET technique, which has been widely applied as a bioanalytical tool, is described. We discuss time-resolved fluorescence (TRF) imaging and flow cytometry technique, using photoluminescent nanoparticles with unique properties for effectively improving selectivity and sensitivity. Based on these techniques, bioanalytical and biomedical application, bioimaging with QD, UCNPs, and Euripium-activated luminescent nanoprobes are covered. Combination of optical property of these luminescent nanoparticles with special functions such as drug delivery, photothermal therapy (PTT), and photodynamic therapy (PDT) is also described.
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http://dx.doi.org/10.1007/978-981-33-6158-4_5DOI Listing
March 2021

Luminescent Nanomaterials (I).

Adv Exp Med Biol 2021 ;1309:67-96

Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.

From molecular probes, also known as fluorophores (typically emitting a longer wavelength than the absorbing wavelength), to inorganic nanoparticles, various light-emitting materials have been actively studied and developed for various applications in life science owing to their superior imaging and sensing ability. Especially after the breakthrough development of quantum dots (QDs), studies have pursued the development of the optical properties and biological applications of luminescent inorganic nanoparticles such as upconversion nanoparticles (UCNPs), metal nanoclusters, carbon dots, and so on. In this review, we first provide a brief explanation about the theoretical background and traditional concepts of molecular fluorophores. Then, currently developed luminescent nanoparticles are described as sensing and imaging platforms from general aspects to technical views.
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http://dx.doi.org/10.1007/978-981-33-6158-4_4DOI Listing
March 2021

Silica Nanoparticles.

Adv Exp Med Biol 2021 ;1309:41-65

Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.

Silica consists of one silicon atom and two oxygen atoms (SiO) and is commonly used in various aspects of daily life. For example, it has been used as glass, insulator, and so on. Nowadays, silica is used as core reagents for fabricating and encapsulating nanoparticles (NPs). In this chapter, the usage of silica in nanotechnology is described. Synthesis and surface modification of silica nanoparticles (SiNPs), including via the Stöber method, reverse microemulsion method, and modified sol-gel method, are illustrated. Then, various NPs with silica encapsulation are explained. At last, the biological applications of those mentioned NPs are described.
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http://dx.doi.org/10.1007/978-981-33-6158-4_3DOI Listing
March 2021

General in Colloidal Nanoparticles.

Adv Exp Med Biol 2021 ;1309:23-40

Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.

It is almost impossible to fabricate size-controlled nanomaterials without full understanding about nanoscience, because nanomaterials sometimes suddenly grow up and precipitated, meanwhile other nanomaterials are disappeared during fabrication process. With this reason, it is necessary to understand the principle theories about nanoscience for fabrication of "well-defined" nanoparticles. This chapter explains basic theories about nanomaterials. And based on the theory, methods for controlling the size of nanoparticles and preventing the aggregation after fabrication are described.
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http://dx.doi.org/10.1007/978-981-33-6158-4_2DOI Listing
March 2021

Introduction of Nanobiotechnology.

Adv Exp Med Biol 2021 ;1309:1-22

Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.

Nano is a fine metric unit which means "one billionth." Nanotechnology is attracting attention as a technological basis to lead the fourth industry. By utilizing synergistic properties obtained from controlling the structure or arrangement of materials at the nanoscale, nanotechnology has evolved rapidly over the past half century and is active in a variety of fields such as materials, pharmaceuticals, and biology. This chapter briefly describes the concept and features of nanotechnology, as well as the preparation, analysis, characterization, and application of nanomaterials. Also, the prospects for nanotechnology along with the nanotoxicity are described.
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http://dx.doi.org/10.1007/978-981-33-6158-4_1DOI Listing
March 2021

Bovine milk extracellular vesicles induce the proliferation and differentiation of osteoblasts and promote osteogenesis in rats.

J Food Biochem 2021 Apr 22;45(4):e13705. Epub 2021 Mar 22.

Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea.

Bone is constantly balanced between the formation of new bone by osteoblasts and the absorption of old bone by osteoclasts. To promote bone growth and improve bone health, it is necessary to promote the proliferation and differentiation of osteoblasts. Although bovine milk is known to exert a beneficial effect on bone formation, the study on the effect of bovine milk extracellular vesicles (EVs) on osteogenesis in osteoblasts is limited. In this study, we demonstrated that bovine milk EVs promoted the proliferation of human osteogenic Saos-2 cells by increasing the expression of cell cycle-related proteins. In addition, bovine milk EVs also induced the differentiation of Saos-2 cells by increasing the expression of RUNX2 and Osterix which are key transcription factors for osteoblast differentiation. Oral administration of milk EVs did not cause toxicity in Sprague-Dawley rats. Furthermore, milk EVs promoted longitudinal bone growth and increased the bone mineral density of the tibia. Our findings suggest that milk EVs could be a safe and powerful applicant for enhancing osteogenesis. PRACTICAL APPLICATIONS: Until now, calcium and vitamin D have been prescribed to promote bone formation or to prevent bone diseases such as osteoporosis. Recently, several studies to find bioactive molecules that regulate cellular functions of osteoblasts or osteoclasts are actively underway. Milk basic proteins and lactoferrin present in milk are known to promote bone formation, but they exist in small quantities and the isolation of these proteins is complicated making mass production difficult. Recently, it has been found that milk contains large quantities of EVs, and that they promote bone formation. Studies on the effect of Milk EVs on osteoblasts during osteogenesis will help in the development of biomaterials for osteogenesis.
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http://dx.doi.org/10.1111/jfbc.13705DOI Listing
April 2021

PrP Aptamer Conjugated-Gold Nanoparticles for Targeted Delivery of Doxorubicin to Colorectal Cancer Cells.

Int J Mol Sci 2021 Feb 17;22(4). Epub 2021 Feb 17.

Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 31151, Korea.

Anticancer drugs, such as fluorouracil (5-FU), oxaliplatin, and doxorubicin (Dox) are commonly used to treat colorectal cancer (CRC); however, owing to their low response rate and adverse effects, the development of efficient drug delivery systems (DDSs) is required. The cellular prion protein PrP, which is a cell surface glycoprotein, has been demonstrated to be overexpressed in CRC, however, there has been no research on the development of PrP-targeting DDSs for targeted drug delivery to CRC. In this study, PrP aptamer (Apt)-conjugated gold nanoparticles (AuNPs) were synthesized for targeted delivery of Dox to CRC. Thiol-terminated PrP-Apt was conjugated to AuNPs, followed by hybridization of its complementary DNA for drug loading. Finally, Dox was loaded onto the AuNPs to synthesize PrP-Apt-functionalized doxorubicin-oligomer-AuNPs (PrP-Apt DOA). The PrP-Apt DOA were spherical nanoparticles with an average diameter of 20 nm. Treatment of CRC cells with PrP-Apt DOA induced reactive oxygen species generation by decreasing catalase and superoxide dismutase activities. In addition, treatment with PrP-Apt DOA inhibited mitochondrial functions by decreasing the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, complex 4 activity, and oxygen consumption rates. Compared to free Dox, PrP-Apt DOA decreased proliferation and increased apoptosis of CRC cells to a greater degree. In this study, we demonstrated that PrP-Apt DOA targeting could effectively deliver Dox to CRC cells. PrP-Apt DOA can be used as a treatment for CRC, and have the potential to replace existing anticancer drugs, such as 5-FU, oxaliplatin, and Dox.
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http://dx.doi.org/10.3390/ijms22041976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922473PMC
February 2021