Publications by authors named "Jonghoon Kim"

71 Publications

Recent Advances in Divergent Synthetic Strategies for Indole-Based Natural Product Libraries.

Molecules 2022 Mar 27;27(7). Epub 2022 Mar 27.

Department of Chemistry, Soongsil University, 369 Sangdo-ro, Seoul 06978, Korea.

Considering the potential bioactivities of natural product and natural product-like compounds with highly complex and diverse structures, the screening of collections and small-molecule libraries for high-throughput screening (HTS) and high-content screening (HCS) has emerged as a powerful tool in the development of novel therapeutic agents. Herein, we review the recent advances in divergent synthetic approaches such as complexity-to-diversity (Ctd) and biomimetic strategies for the generation of structurally complex and diverse indole-based natural product and natural product-like small-molecule libraries.
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http://dx.doi.org/10.3390/molecules27072171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000743PMC
March 2022

Recent Achievements in Total Synthesis for Integral Structural Revisions of Marine Natural Products.

Mar Drugs 2022 Feb 25;20(3). Epub 2022 Feb 25.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Gyeongnam-do, Korea.

A great effort to discover new therapeutic ingredients is often initiated through the discovery of the existence of novel marine natural products. Since substances produced by the marine environment might be structurally more complex and unique than terrestrial natural products, there have been cases of misassignments of their structures despite the availability of modern spectroscopic and computational chemistry techniques. When it comes to refutation to erroneously or tentatively proposed structures empirical preparations through organic chemical synthesis has the greatest contribution along with close and sophiscated inspection of spectroscopic data. Herein, we analyzed the total synthetic studies that have decisively achieved in revelation of errors, ambiguities, or incompleteness of the isolated structures of marine natural products covering the period from 2018 to 2021.
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http://dx.doi.org/10.3390/md20030171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951824PMC
February 2022

Relationship between treatment types and blood-brain barrier disruption in patients with acute ischemic stroke: Two case reports.

World J Clin Cases 2022 Mar;10(7):2351-2356

Medical Interdisciplinary Team, Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, South Korea.

Background: Blood-brain barrier (BBB) disruption plays an important role in the development of neurological dysfunction in ischemic stroke. However, diagnostic modalities that can clearly diagnose the degree of BBB disruption in ischemic stroke are limited. Here, we describe two cases in which the usefulness of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in detecting BBB disruption was evaluated after treatment of acute ischemic stroke using two different methods.

Case Summary: The two patients of similar age and relatively similar cerebral infarction locations were treated conservatively or with thrombectomy, although their sex was different. As a result of analysis by performing DCE-MRI, it was confirmed that BBB disruption was significantly less severe in the patient who underwent thrombectomy ( = 3.3 × 10), whereas the average K of the contralateral hemisphere in both patients was similar (2.4 × 10 min and 2.0 × 10 min). If reperfusion is achieved through thrombectomy, it may indicate that the penumbra can be saved and BBB recovery can be promoted.

Conclusion: Our cases suggest that BBB disruption could be important if BBB permeability is used to guide clinical treatment.
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http://dx.doi.org/10.12998/wjcc.v10.i7.2351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8895168PMC
March 2022

Metal imidazolate sulphate frameworks as a variation of zeolitic imidazolate frameworks.

Chem Commun (Camb) 2022 Mar 1;58(18):2983-2986. Epub 2022 Mar 1.

Department of Chemistry, Soongsil University, Seoul 06978, Republic of Korea.

Sulphate ions can be incorporated into zinc imidazolate frameworks to give rise to zinc imidazolate sulphate frameworks, that is, a square-grid network, a zeolite-like GIS framework, or a porous pillar-layered structure where interlayer octahedral Zn ions connect honeycomb-like layers.
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http://dx.doi.org/10.1039/d1cc07046kDOI Listing
March 2022

Enhanced Chemodynamic Therapy by Cu-Fe Peroxide Nanoparticles: Tumor Microenvironment-Mediated Synergistic Fenton Reaction.

ACS Nano 2022 02 26;16(2):2535-2545. Epub 2022 Jan 26.

Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea.

An urgent need in chemodynamic therapy (CDT) is to achieve high Fenton catalytic efficiency at small doses of CDT agents. However, simple general promotion of the Fenton reaction increases the risk of damaging normal cells along with the cancer cells. Therefore, a tailored strategy to selectively enhance the Fenton reactivity in tumors, for example, by taking advantage of the characteristics of the tumor microenvironment (TME), is in high demand. Herein, a heterogeneous CDT system based on copper-iron peroxide nanoparticles (CFp NPs) is designed for TME-mediated synergistic therapy. CFp NPs degrade under the mildly acidic conditions of TME, self-supply HO, and the released Cu and Fe ions, with their larger portions at lower oxidation states, cooperatively facilitate hydroxyl radical production through a highly efficient catalytic loop to achieve an excellent tumor therapeutic efficacy. This is distinct from previous heterogeneous CDT systems in that the synergism is closely coupled with the Cu-assisted conversion of Fe to Fe rather than their independent actions. As a result, almost complete ablation of tumors at a minimal treatment dose is demonstrated without the aid of any other therapeutic modality. Furthermore, CFp NPs generate O during the catalysis and exhibit a TME-responsive T magnetic resonance imaging contrast enhancement, which are useful for alleviating hypoxia and monitoring of tumors, respectively.
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http://dx.doi.org/10.1021/acsnano.1c09171DOI Listing
February 2022

Inhibition of ACE2-Spike Interaction by an ACE2 Binder Suppresses SARS-CoV-2 Entry.

Angew Chem Int Ed Engl 2022 03 1;61(11):e202115695. Epub 2022 Feb 1.

CRI Center for Chemical Proteomics, Department of Chemistry, Seoul National University, Seoul, 08826, Korea.

The emergence of SARS-CoV-2 variants is a significant concern in developing effective therapeutics and vaccines in the middle of the ongoing COVID-19 pandemic. Here, we have identified a novel small molecule that inhibited the interactions between SARS-CoV-2 spike RBDs and ACE2 by modulating ACE2 without impairing its enzymatic activity necessary for normal physiological functions. Furthermore, the identified compounds suppressed viral infection in cultured cells by inhibiting the entry of ancestral and variant SARS-CoV-2. Our study suggests that targeting ACE2 could be a novel therapeutic strategy to inhibit SARS-CoV-2 entry into host cells and prevent the development of COVID-19.
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http://dx.doi.org/10.1002/anie.202115695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011661PMC
March 2022

Color-Tunable Indolizine-Based Fluorophores and Fluorescent pH Sensor.

Molecules 2021 Dec 21;27(1). Epub 2021 Dec 21.

Department of Chemistry, Soongsil University, Seoul 06978, Korea.

A new fluorescent indolizine-based scaffold was developed using a straightforward synthetic scheme starting from a pyrrole ring. In this fluorescent system, an ,-dimethylamino group in the aryl ring at the C-3 position of indolizine acted as an electron donor and played a crucial role in inducing a red shift in the emission wavelength based on the ICT process. Moreover, various electron-withdrawing groups, such as acetyl and aldehyde, were introduced at the C-7 position of indolizine, to tune and promote the red shift of the emission wavelength, resulting in a color range from blue to orange (462-580 nm). Furthermore, the ICT effect in indolizine fluorophores allowed the design and development of new fluorescent pH sensors of great potential in the field of fluorescence bioimaging and sensors.
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http://dx.doi.org/10.3390/molecules27010012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746752PMC
December 2021

Novel Bi-Modular GH19 Chitinase with Broad pH Stability from a Fibrolytic Intestinal Symbiont of , HY-13.

Biomolecules 2021 11 21;11(11). Epub 2021 Nov 21.

Department of Biotechnology, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34113, Korea.

Endo-type chitinase is the principal enzyme involved in the breakdown of -acetyl-d-glucosamine-based oligomeric and polymeric materials through hydrolysis. The gene (966-bp) encoding a novel endo-type chitinase (ChiJ), which is comprised of an N-terminal chitin-binding domain type 3 and a C-terminal catalytic glycoside hydrolase family 19 domain, was identified from a fibrolytic intestinal symbiont of the earthworm , HY-13. The highest endochitinase activity of the recombinant enzyme (rChiJ: 30.0 kDa) toward colloidal shrimp shell chitin was found at pH 5.5 and 55 °C and was considerably stable in a wide pH range (3.5-11.0). The enzyme exhibited the highest biocatalytic activity (338.8 U/mg) toward ethylene glycol chitin, preferentially degrading chitin polymers in the following order: ethylene glycol chitin > colloidal shrimp shell chitin > colloidal crab shell chitin. The enzymatic hydrolysis of -acetyl-β-d-chitooligosaccharides with a degree of polymerization from two to six and colloidal shrimp shell chitin yielded primarily -diacetyl-β-d-chitobiose together with a small amount of -acetyl-d-glucosamine. The high chitin-degrading ability of inverting rChiJ with broad pH stability suggests that it can be exploited as a suitable biocatalyst for the preparation of -diacetyl-β-d-chitobiose, which has been shown to alleviate metabolic dysfunction associated with type 2 diabetes.
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http://dx.doi.org/10.3390/biom11111735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615386PMC
November 2021

Radiomics-guided deep neural networks stratify lung adenocarcinoma prognosis from CT scans.

Commun Biol 2021 11 12;4(1):1286. Epub 2021 Nov 12.

Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Republic of Korea.

Deep learning (DL) is a breakthrough technology for medical imaging with high sample size requirements and interpretability issues. Using a pretrained DL model through a radiomics-guided approach, we propose a methodology for stratifying the prognosis of lung adenocarcinomas based on pretreatment CT. Our approach allows us to apply DL with smaller sample size requirements and enhanced interpretability. Baseline radiomics and DL models for the prognosis of lung adenocarcinomas were developed and tested using local (n = 617) cohort. The DL models were further tested in an external validation (n = 70) cohort. The local cohort was divided into training and test cohorts. A radiomics risk score (RRS) was developed using Cox-LASSO. Three pretrained DL networks derived from natural images were used to extract the DL features. The features were further guided using radiomics by retaining those DL features whose correlations with the radiomics features were high and Bonferroni-corrected p-values were low. The retained DL features were subject to a Cox-LASSO when constructing DL risk scores (DRS). The risk groups stratified by the RRS and DRS showed a significant difference in training, testing, and validation cohorts. The DL features were interpreted using existing radiomics features, and the texture features explained the DL features well.
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http://dx.doi.org/10.1038/s42003-021-02814-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590002PMC
November 2021

Recent Advances in Fluorescence Imaging by Genetically Encoded Non-canonical Amino Acids.

J Mol Biol 2022 04 20;434(8):167248. Epub 2021 Sep 20.

Department of Chemistry, Pusan National University, Busan 46241, Republic of Korea. Electronic address:

Technical innovations in protein labeling with a fluorophore at the specific residue have played a significant role in studying protein dynamics. The genetic code expansion (GCE) strategy enabled the precise installation of fluorophores at the tailored site of proteins in live cells with minimal perturbation of native functions. Considerable advances have been achieved over the past decades in fluorescent imaging using GCE strategies along with bioorthogonal chemistries. In this review, we discuss advances in the GCE-based strategies to site-specifically introduce fluorophore at a defined position of the protein and their bio-imaging applications.
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http://dx.doi.org/10.1016/j.jmb.2021.167248DOI Listing
April 2022

Novel Anti-Fungal d-Laminaripentaose-Releasing Endo-β-1,3-glucanase with a RICIN-like Domain from HY-13.

Biomolecules 2021 07 22;11(8). Epub 2021 Jul 22.

Department of Biotechnology, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34113, Korea.

Endo-β-1,3-glucanase plays an essential role in the deconstruction of β-1,3-d-glucan polysaccharides through hydrolysis. The gene (1650-bp) encoding a novel, bi-modular glycoside hydrolase family 64 (GH64) endo-β-1,3-glucanase (GluY) with a ricin-type β-trefoil lectin domain (RICIN)-like domain from HY-13 was identified and biocatalytically characterized. The recombinant enzyme (rGluY: 57.5 kDa) displayed the highest degradation activity for laminarin at pH 4.5 and 40 °C, while the polysaccharide was maximally decomposed by its C-terminal truncated mutant enzyme (rGluYΔRICIN: 42.0 kDa) at pH 5.5 and 45 °C. The specific activity (26.0 U/mg) of rGluY for laminarin was 2.6-fold higher than that (9.8 U/mg) of rGluYΔRICIN for the same polysaccharide. Moreover, deleting the C-terminal RICIN domain in the intact enzyme caused a significant decrease (>60%) of its ability to degrade β-1,3-d-glucans such as pachyman and curdlan. Biocatalytic degradation of β-1,3-d-glucans by inverting rGluY yielded predominantly d-laminaripentaose. rGluY exhibited stronger growth inhibition against in a dose-dependent manner than rGluYΔRICIN. The degree of growth inhibition of by rGluY (approximately 1.8 μM) was approximately 80% of the fungal growth. The superior anti-fungal activity of rGluY suggests that it can potentially be exploited as a supplementary agent in the food and pharmaceutical industries.
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http://dx.doi.org/10.3390/biom11081080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394091PMC
July 2021

Effect of annealing environment on the photoelectrochemical water oxidation and electrochemical supercapacitor performance of SnO quantum dots.

Chemosphere 2022 Jan 15;286(Pt 1):131577. Epub 2021 Jul 15.

School of Mechanical Engineering, Yeungnam University, Gyeongsan, 712-749, South Korea. Electronic address:

SnO quantum dots (SQD) were prepared by utilizing the soft-chemical approach. The formed SQD's were annealed in two kinds of environments: air and nitrogen (N). Each annealing environment resulted in significant improvement in the performance of water oxidation and electrochemical supercapacitor performance. The specific capacitance of the SQD's under the N annealing process (SQD-N) shows significantly better electrochemical performance. A specific capacitance of 79.13 F/g was achieved for SQD-N sample by applying a current of 1 mA, which was approximately 1.5 times greater than that of the pristine SQD's. A cycle stability of 99.4% over 5000 cycles was achieved by SQD-N. The process of nitrogen annealing environment brings down the bandgap from 3.37 to 1.9 eV. The SQD-N sample shows the highest photocurrent over SQD and SQD-Air samples. From the LSV study, SQD-N shows the photocurrent density of 4.82 mA/cm, which is 1.43 times greater than pristine SQD sample. The nitrogen-annealing environment provides the optimal environment to tune the average crystallite size and crystallinity nature of SQD's to improve the optical properties like bandgap to enhance the water oxidation and also electrochemical performance.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131577DOI Listing
January 2022

Strategies to Enhance Extracellular Vesicle Production.

Tissue Eng Regen Med 2021 08 18;18(4):513-524. Epub 2021 Jul 18.

Department of Chemistry, Kangwon National University, 1 Gangwondaehakgil, Chuncheon, Gangwon-do, 24341, Republic of Korea.

Extracellular vesicles (EVs) are sub-micrometer lipid vesicles secreted from parental cells with their information such as DNA, RNA, and proteins. EVs can deliver their cargo to recipient cells and regulate the signaling pathway of the recipient cells to determine their destiny. Depending on the cargo of EVs, the recipient cells can be changed into abnormal state or be relieved from diseases. Therefore, EVs has been spotlighted as emerging therapeutics in biomedical research. However, slow EV secretion rate is the major limitation for the clinical applications of EVs. EV secretion is highly environmental dependent and can be regulated by various stimulants such as chemicals, oxygen levels, pH, radiation, starvation, and culture methods. To overcome the limitation of low productivity of EVs, EV stimulation methods have been widely studied and applied to massive EV productions. Another strategy is the synthesis of artificial EVs from cells by physical methods such as nitrogen cavitation, extrusion via porous membrane, and sonication. These physical methods disrupt cellular membrane and reassemble the membrane to lipid vesicles containing proteins or drugs. In this review, we will focus on how EV generation can be enhanced and recent advances in large scale EV generation strategies.
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http://dx.doi.org/10.1007/s13770-021-00364-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325751PMC
August 2021

Rethinking a Non-Predominant Pattern in Invasive Lung Adenocarcinoma: Prognostic Dissection Focusing on a High-Grade Pattern.

Cancers (Basel) 2021 Jun 4;13(11). Epub 2021 Jun 4.

Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM), 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Korea.

Background: Prognostic considerations for non-predominant patterns are necessary because most lung adenocarcinomas (ADCs) have a mixed histologic pattern, and the spectrum of actual prognosis varies widely even among lung ADCs with the same most predominant pattern. We aimed to identify prognostic stratification by second most predominant pattern of lung ADC and to more accurately assess prognostic factors with CT imaging analysis, particularly enhancing non-predominant but high-grade pattern.

Methods: In this prospective study, patients with early-stage lung ADC undergoing curative surgery underwent preoperative dual-energy CT (DECT) and positron emission tomography (PET)/CT. Histopathology of ADC, the most predominant and second most predominant histologic patterns, and preoperative imaging parameters were assessed and correlated with patient survival.

Results: Among the 290 lung ADCs included in the study, 231 (79.7%) were mixed-pathologic pattern. When the most predominant histologic pattern was intermediate-grade, survival curves were significantly different among the three second most predominant subgroups ( = 0.004; low, lepidic; intermediate, acinar and papillary; high, micropapillary and solid). When the second most predominant pattern was high-grade, recurrence risk increased by 4.2-fold compared with the low-grade group ( = 0.005). To predict a non-predominant but high-grade pattern, the non-contrast CT value of tumor was meaningful with a lower HU value associated with the histologic combination of lower grade (low-grade as most predominant and intermediate-grade as second most predominant pattern, OR = 6.15, = 0.005; intermediate-grade as most predominant and high-grade as second most predominant pattern, OR = 0.10, = 0.033). SUVmax of the tumor was associated with the non-predominant but high-grade pattern, especially in the histologic combination of intermediate-high grade (OR = 1.14, = 0.012).

Conclusions: The second most predominant histologic pattern can stratify lung ADC patients according to prognosis. Thus, predicting the malignant potential and establishing treatment policies should not rely only on the most predominant pattern. Moreover, imaging parameters of non-contrast CT value and SUVmax could be useful in predicting a non-predominant but high-grade histologic pattern.
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http://dx.doi.org/10.3390/cancers13112785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200026PMC
June 2021

Identification and Characterization of a Novel, Cold-Adapted d-Xylobiose- and d-Xylose-Releasing Endo-β-1,4-xylanase from an Antarctic Soil Bacterium, sp. PAMC 27433.

Biomolecules 2021 04 30;11(5). Epub 2021 Apr 30.

Industrial Bio-Materials Research Center, KRIBB, Daejeon 34141, Korea.

Endo-β-1,4-xylanase is a key enzyme in the degradation of β-1,4-d-xylan polysaccharides through hydrolysis. A glycoside hydrolase family 10 (GH10) endo-β-1,4-xylanase (XylR) from sp. PAMC 27433, an Antarctic soil bacterium, was identified and functionally characterized. The XylR gene (1122-bp) encoded an acidic protein containing a single catalytic GH10 domain that was 86% identical to that of an uncultured bacterium BLR13 endo-β-1,4-xylanase (ACN58881). The recombinant enzyme (rXylR: 42.0 kDa) showed the highest beechwood xylan-degrading activity at pH 5.5 and 40 °C, and displayed 12% of its maximum activity even at 4 °C. rXylR was not only almost completely inhibited by 5 mM -bromosuccinimide or metal ions (each 1 mM) including Hg, Ca, or Cu but also significantly suppressed by 1 mM Ni, Zn, or Fe. However, its enzyme activity was upregulated (>1.4-fold) in the presence of 0.5% Triton X-100 or Tween 80. The specific activities of rXylR toward beechwood xylan, birchwood xylan, oat spelts xylan, and -nitrophenyl-β-d-cellobioside were 274.7, 103.2, 35.6, and 365.1 U/mg, respectively. Enzymatic hydrolysis of birchwood xylan and d-xylooligosaccharides yielded d-xylose and d-xylobiose as the end products. The results of the present study suggest that rXylR is a novel cold-adapted d-xylobiose- and d-xylose-releasing endo-β-1,4-xylanase.
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http://dx.doi.org/10.3390/biom11050680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147214PMC
April 2021

Enhanced Spin-to-Charge Conversion Efficiency in Ultrathin BiSe Observed by Spintronic Terahertz Spectroscopy.

ACS Appl Mater Interfaces 2021 May 4;13(19):23153-23160. Epub 2021 May 4.

Department of Physics, Yonsei University, Seoul 03722, Republic of Korea.

Owing to their remarkable spin-charge conversion (SCC) efficiency, topological insulators (TIs) are the most attractive candidates for spin-orbit torque generators. The simple method of enhancing SCC efficiency is to reduce the thickness of TI films to minimize the trivial bulk contribution. However, when the thickness reaches the ultrathin regime, the SCC efficiency decreases owing to intersurface hybridization. To overcome these contrary effects, we induced dehybridization of the ultrathin TI film by breaking the inversion symmetry between surfaces. For the TI film grown on an oxygen-deficient transition-metal oxide, the unbonded transition-metal d-orbitals affected only the bottom surface, resulting in asymmetric surface band structures. Spintronic terahertz emission spectroscopy, an emerging tool for investigating the SCC characteristics, revealed that the resulting SCC efficiency in symmetry-broken ultrathin BiSe was enhanced by up to ∼2.4 times.
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http://dx.doi.org/10.1021/acsami.1c03168DOI Listing
May 2021

Overview of Syntheses and Molecular-Design Strategies for Tetrazine-Based Fluorogenic Probes.

Molecules 2021 Mar 26;26(7). Epub 2021 Mar 26.

Department of Molecular Science and Technology, Ajou University, Suwon 16499, Korea.

Various bioorthogonal chemistries have been used for fluorescent imaging owing to the advantageous reactions they employ. Recent advances in bioorthogonal chemistry have revolutionized labeling strategies for fluorescence imaging, with inverse electron demand Diels-Alder (iEDDA) reactions in particular attracting recent attention owing to their fast kinetics and excellent specificity. One of the most interesting features of the iEDDA labeling strategy is that tetrazine-functionalized dyes are known to act as fluorogenic probes. In this review, we will focus on the synthesis, molecular-design strategies, and bioimaging applications of tetrazine-functionalized fluorogenic probes. Traditional Pinner reaction and "Pinner-like" reactions for tetrazine synthesis are discussed here, as well as metal-catalyzed C-C bond formations with convenient tetrazine intermediates and the fabrication of tetrazine-conjugated fluorophores. In addition, four different quenching mechanisms for tetrazine-modified fluorophores are presented.
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http://dx.doi.org/10.3390/molecules26071868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037913PMC
March 2021

Predicting amyloid positivity in patients with mild cognitive impairment using a radiomics approach.

Sci Rep 2021 03 26;11(1):6954. Epub 2021 Mar 26.

Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Korea.

Predicting amyloid positivity in patients with mild cognitive impairment (MCI) is crucial. In the present study, we predicted amyloid positivity with structural MRI using a radiomics approach. From MR images (including T1, T2 FLAIR, and DTI sequences) of 440 MCI patients, we extracted radiomics features composed of histogram and texture features. These features were used alone or in combination with baseline non-imaging predictors such as age, sex, and ApoE genotype to predict amyloid positivity. We used a regularized regression method for feature selection and prediction. The performance of the baseline non-imaging model was at a fair level (AUC = 0.71). Among single MR-sequence models, T1 and T2 FLAIR radiomics models also showed fair performances (AUC for test = 0.71-0.74, AUC for validation = 0.68-0.70) in predicting amyloid positivity. When T1 and T2 FLAIR radiomics features were combined, the AUC for test was 0.75 and AUC for validation was 0.72 (p vs. baseline model < 0.001). The model performed best when baseline features were combined with a T1 and T2 FLAIR radiomics model (AUC for test = 0.79, AUC for validation = 0.76), which was significantly better than those of the baseline model (p < 0.001) and the T1 + T2 FLAIR radiomics model (p < 0.001). In conclusion, radiomics features showed predictive value for amyloid positivity. It can be used in combination with other predictive features and possibly improve the prediction performance.
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http://dx.doi.org/10.1038/s41598-021-86114-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997887PMC
March 2021

Delayed cranial nerve palsy after successful coil embolization in cavernous sinus lesion.

J Cerebrovasc Endovasc Neurosurg 2021 Mar 26;23(1):35-40. Epub 2021 Jan 26.

Department of Neurosurgery, Yeungnam University Medical Center and College of Medicine, Daegu, Korea.

Cavernous sinus (CS) lesion is hard to access by surgical approach. With the development of endovascular technique, neurointerventional therapy is an alternative modality for CS lesions. This endovascular technique has been widely used for the past decade, avoiding the risks associated with surgical treatment. However, complications can still arise from coil embolization. Although immediate complication associate with embolic event or mass effect has been well described, but delayed (>1 year from treatment) nerve palsy after coil embolization is rare. We report two cases of delayed cranial nerve palsy after successful endovascular coil embolization in CS lesion.
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http://dx.doi.org/10.7461/jcen.2021.E2020.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041510PMC
March 2021

Enhanced solar-light-driven photocatalytic and photoelectrochemical properties of zinc tungsten oxide nanorods anchored on bismuth tungsten oxide nanoflakes.

Chemosphere 2021 Apr 16;268:129346. Epub 2020 Dec 16.

School of Mechanical Engineering, Yeungnam University, Gyeongsan, 712-749, Republic of Korea. Electronic address:

At present, sustainable water supply and energy generation are the most important challenges faced by humankind globally. Thus, it is crucial to progress ecological techniques for sustainable removal of organic pollutants from wastewater and generation of hydrogen as an alternative to fossil fuels. In this study, zinc tungsten oxide (ZnWO) nanorods, bismuth tungsten oxide (BiWO) nanoflakes, and BiWO/ZnWO (BO-ZO) nanocomposites were prepared via a simple hydrothermal approach. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, diffuse reflectance spectroscopy, and electrochemical analyses were conducted to confirm the formation of the BO-ZO heterostructure. The structural and morphological analyses revealed that the ZnWO nanorods were moderately dispersed on the BiWO nanoflakes. The bandgap tuning of BO-ZO nanocomposite confirmed the establishment of the heterostructure with band bending properties. The BO-ZO nanocomposite could degrade 99.52% of methylene blue (MB) within 60 min upon solar-light illumination. The photoelectrochemical (PEC) measurement results showed that the BO-ZO nanocomposite showed low charge-transfer resistance and high photocurrent response with good stability. The BO-ZO photoanode showed a low charge-transfer resistance of 35.33 Ω and high photocurrent density of 0.1779 mA/cm in comparison with Ag/AgCl in a 0.1 M NaSO electrolyte under solar-light illumination. The MB photocatalytic degradation and PEC water oxidation mechanisms of the nanocomposite were investigated.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129346DOI Listing
April 2021

Phenotypic Discovery of Neuroprotective Agents by Regulation of Tau Proteostasis via Stress-Responsive Activation of PERK Signaling.

Angew Chem Int Ed Engl 2021 01 23;60(4):1831-1838. Epub 2020 Dec 23.

CRI Center for Chemical Proteomics, Department of Chemistry, Seoul National University, Seoul, 08826, Korea.

Tau protein aggregates are a recognized neuropathological feature in Alzheimer's disease as well as many other neurodegenerative disorders, known as tauopathies. The development of tau-targeting therapies is therefore extremely important but efficient strategies or protein targets are still unclear. Here, we performed a cell-based phenotypic screening under endoplasmic reticulum (ER) stress conditions and identified a small molecule, SB1617, capable of suppressing abnormal tau protein aggregation. By applying label-free target identification technology, we revealed that the transient enhancement of protein kinase-like endoplasmic reticulum kinase (PERK) signaling pathway through the inhibition of stress-responsive SB1617 targets, PDIA3 and DNAJC3, is an effective strategy for regulating proteostasis in tauopathies. The molecular mechanism and the promising efficacy of SB1617 were demonstrated in neuronal cells and a mouse model with traumatic brain injury, a tauopathy known to involve ER stress.
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http://dx.doi.org/10.1002/anie.202013915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898623PMC
January 2021

Pre-Planned Cranioplasty Using Computer-Assisted Designed Temporalis Muscle Augmentation in Patients With Decompressive Craniectomy Involving Resection of the Temporalis Muscle.

J Craniofac Surg 2021 Jan-Feb 01;32(1):e60-e62

Department of Neurosurgery, Yeungnam University Medical Center and Medical School, Daegu, South Korea.

Background: Decompressive craniectomy (DC) is the last-resort surgical procedure to reduce intracranial pressure and prevent secondary brain injury. Additional resection of the temporalis muscle and fascia can achieve a higher extracranial herniation volume compared to the standard DC technique at the expense of cosmetic problems for the patients. Various methods have been used to augment temporal fossa hollowing.

Methods: To improve the cosmetic outcome, the authors report a patient who had a skull defect restored using a precisely shaped implant engineered via a computer using the opposite temporalis muscle as a mirror image. Polyether-ether-ketone cranioplasty was performed for the 52-year-old man with temporal hollowing after DC with resection of the temporalis muscle and fascia, due to a ruptured cerebral arteriovenous fistula.

Results: The shape of the patient's surgical side was restored and not asymmetrical. The patient was very satisfied.

Conclusion: In the case of cranioplasty (CP) in patients with DC with resection of the temporalis muscle, CP with implants that include the opposite muscle may increase patient satisfaction without the risk of additional complications.
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http://dx.doi.org/10.1097/SCS.0000000000006928DOI Listing
June 2021

Nanovesicles derived from iron oxide nanoparticles-incorporated mesenchymal stem cells for cardiac repair.

Sci Adv 2020 05 1;6(18):eaaz0952. Epub 2020 May 1.

School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea.

Because of poor engraftment and safety concerns regarding mesenchymal stem cell (MSC) therapy, MSC-derived exosomes have emerged as an alternative cell-free therapy for myocardial infarction (MI). However, the diffusion of exosomes out of the infarcted heart following injection and the low productivity limit the potential of clinical applications. Here, we developed exosome-mimetic extracellular nanovesicles (NVs) derived from iron oxide nanoparticles (IONPs)-incorporated MSCs (IONP-MSCs). The retention of injected IONP-MSC-derived NVs (IONP-NVs) within the infarcted heart was markedly augmented by magnetic guidance. Furthermore, IONPs significantly increased the levels of therapeutic molecules in IONP-MSCs and IONP-NVs, which can reduce the concern of low exosome productivity. The injection of IONP-NVs into the infarcted heart and magnetic guidance induced an early shift from the inflammation phase to the reparative phase, reduced apoptosis and fibrosis, and enhanced angiogenesis and cardiac function recovery. This approach can enhance the therapeutic potency of an MSC-derived NV therapy.
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http://dx.doi.org/10.1126/sciadv.aaz0952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195131PMC
May 2020

Targeted Delivery of Iron Oxide Nanoparticle-Loaded Human Embryonic Stem Cell-Derived Spherical Neural Masses for Treating Intracerebral Hemorrhage.

Int J Mol Sci 2020 May 22;21(10). Epub 2020 May 22.

Department of Neurology, Seoul National University Hospital, Seoul 03080, Korea.

This study evaluated the potential of iron oxide nanoparticle-loaded human embryonic stem cell (ESC)-derived spherical neural masses (SNMs) to improve the transportation of stem cells to the brain, ameliorate brain damage from intracerebral hemorrhage (ICH), and recover the functional status after ICH under an external magnetic field of a magnet attached to a helmet. At 24 h after induction of ICH, rats were randomly separated into three experimental groups: ICH with injection of phosphate-buffered saline (PBS group), ICH with intravenous injection of magnetosome-like ferrimagnetic iron oxide nanocubes (FION)-labeled SNMs (SNMs* group), and ICH with intravenous injection of FION-labeled SNMs followed by three days of external magnetic field exposure for targeted delivery by a magnet-embedded helmet (SNMs*+Helmet group). On day 3 after ICH induction, an increased Prussian blue-stained area and decreased swelling volume were observed in the SNMs*+Helmet group compared with that of the other groups. A significantly decreased recruitment of macrophages and neutrophils and a downregulation of pro-inflammatory cytokines followed by improved neurological function three days after ICH were observed in the SNMs*+Helmet group. Hemispheric atrophy at six weeks after ICH was significantly decreased in the SNMs*+Helmet group compared with that of the PBS group. In conclusion, we have developed a targeted delivery system using FION tagged to stem cells and a magnet-embedded helmet. The targeted delivery of SNMs might have the potential for developing novel therapeutic strategies for ICH.
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http://dx.doi.org/10.3390/ijms21103658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279437PMC
May 2020

Enhanced Photoinduced Carrier Generation Efficiency through Surface Band Bending in Topological Insulator BiSe Thin Films by the Oxidized Layer.

ACS Appl Mater Interfaces 2020 Jun 27;12(23):26649-26658. Epub 2020 May 27.

Department of Physics, Yonsei University, Seoul 03722, Republic of Korea.

Topological insulators (TIs) have become popular in the field of optoelectronic devices because of their broadband and high-sensitivity properties, which are attributed to the narrow band gap of the bulk state and high mobility of the Dirac surface state. Although perfectly grown TIs are known to exhibit strong stability against oxidation, in most cases, the existence of vacancy defects in TIs reacts to air and the characteristics of TIs is affected by oxidation. Therefore, changes in the band structure and electrical characteristics by oxidation should be considered. A significant change occurs because of the oxidation; however, the dependence of the photoresponse of TIs on oxidation has not been studied in detail. In this study, the photoresponsivity of oxidized BiSe films is enhanced, rather than degraded, after oxidation in air for 24 h, resulting in a maximum responsivity of 140 mA W. This responsivity is substantially higher than previously reported values for BiSe. Furthermore, a change in the photoresponse time of BiSe due to air exposure is systematically observed. Based on variations in the Fermi level and work function, using photoelectron spectroscopy, it is confirmed that the responsivity is improved from the junction effect of the Bi-based surface oxidized layer.
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http://dx.doi.org/10.1021/acsami.0c05165DOI Listing
June 2020

Mesenchymal stem cell-derived magnetic extracellular nanovesicles for targeting and treatment of ischemic stroke.

Biomaterials 2020 06 6;243:119942. Epub 2020 Mar 6.

School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea; Interdisciplinary Program of Bioengineering, Seoul National University, Seoul, 08826, Republic of Korea; Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address:

Exosomes and extracellular nanovesicles (NV) derived from mesenchymal stem cells (MSC) may be used for the treatment of ischemic stroke owing to their multifaceted therapeutic benefits that include the induction of angiogenesis, anti-apoptosis, and anti-inflammation. However, the most serious drawback of using exosomes and NV for ischemic stroke is the poor targeting on the ischemic lesion of brain after systemic administration, thereby yielding a poor therapeutic outcome. In this study, we show that magnetic NV (MNV) derived from iron oxide nanoparticles (IONP)-harboring MSC can drastically improve the ischemic-lesion targeting and the therapeutic outcome. Because IONP stimulated expressions of therapeutic growth factors in the MSC, MNV contained greater amounts of those therapeutic molecules compared to NV derived from naive MSC. Following the systemic injection of MNV into transient middle-cerebral-artery-occlusion (MCAO)-induced rats, the magnetic navigation increased the MNV localization to the ischemic lesion by 5.1 times. The MNV injection and subsequent magnetic navigation promoted the anti-inflammatory response, angiogenesis, and anti-apoptosis in the ischemic brain lesion, thereby yielding a considerably decreased infarction volume and improved motor function. Overall, the proposed MNV approach may overcome the major drawback of the conventional MSC-exosome therapy or NV therapy for the treatment of ischemic stroke.
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http://dx.doi.org/10.1016/j.biomaterials.2020.119942DOI Listing
June 2020

Prognostic Prediction of Dysphagia by Analyzing the Corticobulbar Tract in the Early Stage of Intracerebral Hemorrhage.

Dysphagia 2020 12 10;35(6):985-992. Epub 2020 Feb 10.

Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, 317-1, Daemyung dong, Namgu, Taegu, 705-717, Republic of Korea.

We investigated the predictive value of the corticobulbar tract (CBT) for dysphagia using diffusion tensor tractography in the early stage of intracerebral hemorrhage (ICH) for dysphagia. Forty-two patients with spontaneous ICH ± intraventricular hemorrhage (IVH) and 22 control subjects were recruited. The patients were classified into three groups: group A-could remove nasogastric tube (NGT) in the acute stage of ICH, group B-could remove NGT within 6 months after onset, and group C-could not remove NGT until 6 months after onset. The CBT were reconstructed, and fractional anisotropy (FA) and tract volume (TV) values were determined. The FA of the CBT in the affected hemisphere in group A was lower than in the control group (p < 0.05). The FA and TV of the CBT in the affected hemisphere in group B were lower than those in the control group (p < 0.05). In group C, the FA and TV in the affected hemisphere and unaffected hemispheres were lower than in the control group (p < 0.05). The TV of the CBT in the affected hemisphere in group B showed a moderate negative correlation with the length of time until NGT removal (r = 0.430, p < 0.05). We found that patients with CBT injuries in both hemispheres were not able to remove the NGT until 6 months after onset, whereas patients who were injured only in the affected hemisphere were able to remove NGT within 6 months of onset. The severity of injury to the CBT in the affected hemisphere appeared to be related to the length of time until NGT removal.
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http://dx.doi.org/10.1007/s00455-020-10093-3DOI Listing
December 2020

Flexible, sticky, and biodegradable wireless device for drug delivery to brain tumors.

Nat Commun 2019 11 15;10(1):5205. Epub 2019 Nov 15.

Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, 08826, Republic of Korea.

Implantation of biodegradable wafers near the brain surgery site to deliver anti-cancer agents which target residual tumor cells by bypassing the blood-brain barrier has been a promising method for brain tumor treatment. However, further improvement in the prognosis is still necessary. We herein present novel materials and device technologies for drug delivery to brain tumors, i.e., a flexible, sticky, and biodegradable drug-loaded patch integrated with wireless electronics for controlled intracranial drug delivery through mild-thermic actuation. The flexible and bifacially-designed sticky/hydrophobic device allows conformal adhesion on the brain surgery site and provides spatially-controlled and temporarily-extended drug delivery to brain tumors while minimizing unintended drug leakage to the cerebrospinal fluid. Biodegradation of the entire device minimizes potential neurological side-effects. Application of the device to the mouse model confirms tumor volume suppression and improved survival rate. Demonstration in a large animal model (canine model) exhibited its potential for human application.
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http://dx.doi.org/10.1038/s41467-019-13198-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858362PMC
November 2019

Deep Tumor Penetration of Drug-Loaded Nanoparticles by Click Reaction-Assisted Immune Cell Targeting Strategy.

J Am Chem Soc 2019 09 22;141(35):13829-13840. Epub 2019 Aug 22.

Center for Nanoparticle Research , Institute for Basic Science (IBS) , Seoul 08826 , Republic of Korea.

Nanoparticles have been extensively used to deliver therapeutic drugs to tumor tissues through the extravasation of a leaky vessel via enhanced permeation and retention effect (EPR, passive targeting) or targeted interaction of tumor-specific ligands (active targeting). However, the therapeutic efficacy of drug-loaded nanoparticles is hampered by its heterogeneous distribution owing to limited penetration in tumor tissue. Inspired by the fact that cancer cells can recruit inflammatory immune cells to support their survival, we developed a click reaction-assisted immune cell targeting (CRAIT) strategy to deliver drug-loaded nanoparticles deep into the avascular regions of the tumor. Immune cell-targeting CD11b antibodies are modified with -cyclooctene to enable bioorthogonal click chemistry with mesoporous silica nanoparticles functionalized with tetrazines (MSNs-Tz). Sequential injection of modified antibodies and MSNs-Tz at intervals of 24 h results in targeted conjugation of the nanoparticles onto CD11b myeloid cells, which serve as active vectors into tumor interiors. We show that the CRAIT strategy allows the deep tumor penetration of drug-loaded nanoparticles, resulting in enhanced therapeutic efficacy in an orthotopic 4T1 breast tumor model. The CRAIT strategy does not require ex vivo manipulation of cells and can be applied to various types of cells and nanovehicles.
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http://dx.doi.org/10.1021/jacs.9b04621DOI Listing
September 2019

Synergistic Oxygen Generation and Reactive Oxygen Species Scavenging by Manganese Ferrite/Ceria Co-decorated Nanoparticles for Rheumatoid Arthritis Treatment.

ACS Nano 2019 03 7;13(3):3206-3217. Epub 2019 Mar 7.

Center for Nanoparticle Research , Institute for Basic Science (IBS) , Seoul 08826 , Republic of Korea.

Poor O supply to the infiltrated immune cells in the joint synovium of rheumatoid arthritis (RA) up-regulates hypoxia-inducible factor (HIF-1α) expression and induces reactive oxygen species (ROS) generation, both of which exacerbate synovial inflammation. Synovial inflammation in RA can be resolved by eliminating pro-inflammatory M1 macrophages and inducing anti-inflammatory M2 macrophages. Because hypoxia and ROS in the RA synovium play a crucial role in the induction of M1 macrophages and reduction of M2 macrophages, herein, we develop manganese ferrite and ceria nanoparticle-anchored mesoporous silica nanoparticles (MFC-MSNs) that can synergistically scavenge ROS and produce O for reducing M1 macrophage levels and inducing M2 macrophages for RA treatment. MFC-MSNs exhibit a synergistic effect on O generation and ROS scavenging that is attributed to the complementary reaction of ceria nanoparticles (NPs) that can scavenge intermediate hydroxyl radicals generated by manganese ferrite NPs in the process of O generation during the Fenton reaction, leading to the efficient polarization of M1 to M2 macrophages both in vitro and in vivo. Intra-articular administration of MFC-MSNs to rat RA models alleviated hypoxia, inflammation, and pathological features in the joint. Furthermore, MSNs were used as a drug-delivery vehicle, releasing the anti-rheumatic drug methotrexate in a sustained manner to augment the therapeutic effect of MFC-MSNs. This study highlights the therapeutic potential of MFC-MSNs that simultaneously generate O and scavenge ROS, subsequently driving inflammatory macrophages to the anti-inflammatory subtype for RA treatment.
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http://dx.doi.org/10.1021/acsnano.8b08785DOI Listing
March 2019
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