Publications by authors named "Jongmin Kim"

154 Publications

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

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

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

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

Download full-text PDF

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

Synthetic logic circuits using RNA aptamer against T7 RNA polymerase.

Biotechnol J 2021 Apr 4:e2000449. Epub 2021 Apr 4.

Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.

Recent advances in nucleic acids engineering introduced several RNA-based regulatory components for synthetic gene circuits, expanding the toolsets to engineer organisms. In this work, we designed genetic circuits implementing an RNA aptamer previously described to have the capability of binding to the T7 RNA polymerase and inhibiting its activity in vitro. We first demonstrated the utility of the RNA aptamer in combination with programmable synthetic transcription networks in vitro. As a step to quickly assess the feasibility of aptamer functions in vivo, we tested the aptamer and its sequence variants in the cell-free expression system, verifying the aptamer functionality in the cell-free testbed. The expression of aptamer in E. coli demonstrated control over GFP expression driven by T7 RNA polymerase, indicating its ability to serve as building blocks for logic circuits and transcriptional cascades. This work elucidates the potential of T7 RNA polymerase aptamer as regulators for synthetic biological circuits and metabolic engineering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/biot.202000449DOI Listing
April 2021

Signal amplification and optimization of riboswitch-based hybrid inputs by modular and titratable toehold switches.

J Biol Eng 2021 Mar 19;15(1):11. Epub 2021 Mar 19.

Department of Chemical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk, 37673, South Korea.

Background: Synthetic biological circuits are widely utilized to control microbial cell functions. Natural and synthetic riboswitches are attractive sensor modules for use in synthetic biology applications. However, tuning the fold-change of riboswitch circuits is challenging because a deep understanding of the riboswitch mechanism and screening of mutant libraries is generally required. Therefore, novel molecular parts and strategies for straightforward tuning of the fold-change of riboswitch circuits are needed.

Results: In this study, we devised a toehold switch-based modulator approach that combines a hybrid input construct consisting of a riboswitch and transcriptional repressor and de-novo-designed riboregulators named toehold switches. First, the introduction of a pair of toehold switches and triggers as a downstream signal-processing module to the hybrid input for coenzyme B resulted in a functional riboswitch circuit. Next, several optimization strategies that focused on balancing the expression levels of the RNA components greatly improved the fold-change from 260- to 887-fold depending on the promoter and host strain. Further characterizations confirmed low leakiness and high orthogonality of five toehold switch pairs, indicating the broad applicability of this strategy to riboswitch tuning.

Conclusions: The toehold switch-based modulator substantially improved the fold-change compared to the previous sensors with only the hybrid input construct. The programmable RNA-RNA interactions amenable to in silico design and optimization can facilitate further development of RNA-based genetic modulators for flexible tuning of riboswitch circuitry and synthetic biosensors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13036-021-00261-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977183PMC
March 2021

Full methylation of H3K27 by PRC2 is dispensable for initial embryoid body formation but required to maintain differentiated cell identity.

Development 2021 Apr 15;148(7). Epub 2021 Apr 15.

Department of Molecular Biology, Massachusetts General Hospital Research Institute, Massachusetts General Hospital, Boston, MA 02114, USA.

Polycomb repressive complex 2 (PRC2) catalyzes methylation of histone H3 on lysine 27 and is required for normal development of complex eukaryotes. The nature of that requirement is not clear. H3K27me3 is associated with repressed genes, but the modification is not sufficient to induce repression and, in some instances, is not required. We blocked full methylation of H3K27 with both a small molecule inhibitor, GSK343, and by introducing a point mutation into EZH2, the catalytic subunit of PRC2, in the mouse CJ7 cell line. Cells with substantively decreased H3K27 methylation differentiate into embryoid bodies, which contrasts with EZH2 null cells. PRC2 targets had varied requirements for H3K27me3, with a subset that maintained normal levels of repression in the absence of methylation. The primary cellular phenotype of blocked H3K27 methylation was an inability of altered cells to maintain a differentiated state when challenged. This phenotype was determined by H3K27 methylation in embryonic stem cells through the first 4 days of differentiation. Full H3K27 methylation therefore was not necessary for formation of differentiated cell states during embryoid body formation but was required to maintain a stable differentiated state.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1242/dev.196329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077505PMC
April 2021

Making Waxy Salts in Water: Synthetic Control of Hydrophobicity for Anion-Induced and Aggregation-Enhanced Light Emission.

Angew Chem Int Ed Engl 2021 May 30;60(19):10858-10864. Epub 2021 Mar 30.

Department of Chemistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea.

We show that multipodal polycationic receptors function as anion-responsive light-emitters in water. Prevailing paradigms utilize rigid holes and cavities for ion recognition. We instead built open amphiphilic scaffolds that trigger polar-to-nonpolar environment transitions around cationic fluorophores upon anion complexation. This ion-pairing and aggregation event produces a dramatic enhancement in the emission intensity, as demonstrated by perchlorate as a non-spherical hydrophobic anion model. A synergetic interplay of C-H⋅⋅⋅anion hydrogen bonding and tight anion-π contacts underpins this supramolecular phenomenon. By changing the aliphatic chain length, we demonstrate that the response profile and threshold of this signaling event can be controlled at the molecular level. With appropriate molecular design, inherently weak, ill-defined, and non-directional van der Waals interaction enables selective, sensitive, and tunable recognition in water.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202100729DOI Listing
May 2021

Simultaneous ipsilateral distal radius and radial head fractures: Two case reports of radius bipolar fracture.

Medicine (Baltimore) 2021 Jan;100(3):e24036

Department of Orthopaedic Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea.

Rationale: Distal radius fracture with simultaneous ipsilateral radial head fracture is a very rare pattern of injury. This type of injury is referred to as 'radius bipolar fracture'. Treatments for this injury pattern can be challenging because both the wrist and elbow need to be considered. There are currently no guidelines for the treatment of this specific type of injury. We report two cases of this unusual pattern of injury treated in our hospital.

Patient Concerns: Case 1 was a 78-year-old female patient and case 2 was a 19-year-old female patient who visited our emergency department with left elbow and wrist pain after slipping and falling.

Diagnosis: Plain radiography and computed tomography revealed radius bipolar fracture. Case 1 had an AO type C3 distal radius fracture, a Mason type III radial head fracture. Case 2 had an AO type B2 undisplaced distal radius fracture and a Mason type III radial head fracture.

Interventions: In case 1, open reduction and internal fixation (ORIF) was performed for the distal radius fracture and radial head replacement arthroplasty for the radial head fracture. In case 2, distal radius fracture was treated conservatively and ORIF was performed for the radial head fracture.

Outcomes: Bony union as achieved in both cases. At 1-year follow-up, case 1 showed slight limited range of motion of the wrist. Case 2 showed no radius shortening and full range of motion of the wrist and elbow. The Quick disabilities of the arm, shoulder and hand score was 18 and 16, respectively.

Lessons: After this type of injury, the radius length can be changed, and as a result, ulnar variance can be affected. When radial head replaced is considered, it would be better to operate on the wrist first, and then perform radial head replacement. In this way, radiocapitellar overstuffing or instability can be prevented. However, if ORIF is planned for proximal radius fracture, either the proximal or distal radius can be fixed first. Surgeons should try to preserve radial length during treatment to optimize patient outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000024036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837832PMC
January 2021

Wearable plasmonic-metasurface sensor for noninvasive and universal molecular fingerprint detection on biointerfaces.

Sci Adv 2021 Jan 22;7(4). Epub 2021 Jan 22.

College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China.

Wearable sensing technology is an essential link to future personalized medicine. However, to obtain a complete picture of human health, it is necessary but challenging to track multiple analytes inside the body simultaneously. Here, we present a wearable plasmonic-electronic sensor with "universal" molecular recognition ability. Flexible plasmonic metasurface with surface-enhanced Raman scattering (SERS)-activity is introduced as the fundamental sensing component in a wearable sensor since we solved the technical challenge of maintaining the plasmonic activities of their brittle nanostructures under various deformations. Together with a flexible electronic sweat extraction system, our sensor can noninvasively extract and "fingerprint" analytes inside the body based on their unique SERS spectra. As a proof-of-concept example, we successfully monitored the variation of trace-amounts drugs inside the body and obtained an individual's drug metabolic profile. Our sensor bridges the existing gap in wearable sensing technology by providing a universal, sensitive molecular tracking means to assess human health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abe4553DOI Listing
January 2021

Development of 3D Printed Bruch's Membrane-Mimetic Substance for the Maturation of Retinal Pigment Epithelial Cells.

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

Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea.

Retinal pigment epithelium (RPE) is a monolayer of the pigmented cells that lies on the thin extracellular matrix called Bruch's membrane. This monolayer is the main component of the outer blood-retinal barrier (BRB), which plays a multifunctional role. Due to their crucial roles, the damage of this epithelium causes a wide range of diseases related to retinal degeneration including age-related macular degeneration, retinitis pigmentosa, and Stargardt disease. Unfortunately, there is presently no cure for these diseases. Clinically implantable RPE for humans is under development, and there is no practical examination platform for drug development. Here, we developed porcine Bruch's membrane-derived bioink (BM-ECM). Compared to conventional laminin, the RPE cells on BM-ECM showed enhanced functionality of RPE. Furthermore, we developed the Bruch's membrane-mimetic substrate (BMS) via the integration of BM-ECM and 3D printing technology, which revealed structure and extracellular matrix components similar to those of natural Bruch's membrane. The developed BMS facilitated the appropriate functions of RPE, including barrier and clearance functions, the secretion of anti-angiogenic growth factors, and enzyme formation for phototransduction. Moreover, it could be used as a basement frame for RPE transplantation. We established BMS using 3D printing technology to grow RPE cells with functions that could be used for an in vitro model and RPE transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22031095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865340PMC
January 2021

Application of Gelatin Bioinks and Cell-Printing Technology to Enhance Cell Delivery Capability for 3D Liver Fibrosis-on-a-Chip Development.

ACS Biomater Sci Eng 2020 04 4;6(4):2469-2477. Epub 2020 Mar 4.

Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Hyogok-dong, Nam-gu, Pohang-si, Gyeongsangbuk-do, 37673, South Korea.

Liver fibrosis is a critical liver disease which can lead to liver cirrhosis, cancer, and liver failure. Among various etiological factors, activated stellate cells are a major factor that can induce liver fibrosis. Several studies have presented models to identify drugs for liver fibrosis; however, there are still limitations in terms of the 2D culture conditions, random co-culture of liver cells, and lack of extracellular matrix components. Therefore, a 3D liver fibrosis-on-a-chip was developed with three liver cell types (hepatocytes, activated stellate cells, and endothelial cells) using a novel cell-printing technique with gelatin bioinks, which were used to deliver each nonparenchymal liver cell type as a multilayer construct. Liver fibrosis-specific gene expression, collagen accumulation, cell apoptosis, and reduced liver functions caused by activated stellate cells were also evaluated. Furthermore, previously reported chemicals were added to the 3D liver fibrosis-on-a-chip to examine the downregulation of activated hepatic stellate cells. In conclusion, the developed 3D liver fibrosis-on-a-chip could be used as a potential model in the research field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsbiomaterials.9b01735DOI Listing
April 2020

MiR-146a Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells.

Genes (Basel) 2020 Dec 30;12(1). Epub 2020 Dec 30.

Research Institute for Women's Health, Sookmyung Women's University, Seoul 04310, Korea.

Cancer metastasis is the primary cause of cancer-related death and metastatic cancer has circulating-tumor cells (CTCs), which circulate in the bloodstream before invading other organs. Thus, understanding the precise role of CTCs may provide new insights into the metastasis process and reduce cancer mortality. However, the molecular characteristics of CTCs are not well understood due to a lack of number of CTCs. Therefore, suspension cells were generated from MDA-MB-468 cells to mimic CTCs, and we investigate the microRNA (miRNA)-dependent molecular networks and their role in suspension cells. Here, we present an integrated analysis of mRNA and miRNA sequencing data for suspension cell lines, through comparison with adherent cells. Among the differentially regulated miRNA-mRNAs axes, we focus on the miR-146a-Neuropilin2 (NRP2) axis, which is known to influence tumor aggressiveness. We show that miR-146a directly regulates NRP2 expression and inhibits Semaphorin3C (SEMA3C) signaling. Functional studies reveal that miR-146a represses SEMA3C-induced invasion and proliferation by targeting NRP2. Finally, high-NRP2 is shown to be associated with poor outcomes in breast cancer patients. This study identifies the key role of the miR-146a-NRP2 signaling axis that is critical for the regulation of migration and invasion in CTC-mimicking cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes12010045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824086PMC
December 2020

MicroRNA 34a-AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells.

Genes (Basel) 2020 Dec 23;12(1). Epub 2020 Dec 23.

Division of Biological Sciences, Sookmyung Women's University, Seoul 04310, Korea.

Targeting the tumor vasculature is an attractive strategy for cancer treatment. However, the tumor vasculature is heterogeneous, and the mechanisms involved in the neovascularization of tumors are highly complex. Vasculogenic mimicry (VM) refers to the formation of vessel-like structures by tumor cells, which can contribute to tumor neovascularization, and is closely related to metastasis and a poor prognosis. Here, we report a novel function of AXL receptor tyrosine kinase (AXL) in the regulation of VM formation in breast cancer cells. MDA-MB-231 cells exhibited VM formation on Matrigel cultures, whereas MCF-7 cells did not. Moreover, AXL expression was positively correlated with VM formation. Pharmacological inhibition or AXL knockdown strongly suppressed VM formation in MDA-MB-231 cells, whereas the overexpression of AXL in MCF-7 cells promoted VM formation. In addition, AXL knockdown regulated epithelial-mesenchymal transition (EMT) features, increasing cell invasion and migration in MDA-MB-231 cells. Finally, the overexpression of microRNA-34a (miR-34a), which is a well-described EMT-inhibiting miRNA and targets AXL, inhibited VM formation, migration, and invasion in MDA-MB 231 cells. These results identify a miR-34a-AXL axis that is critical for the regulation of VM formation and may serve as a therapeutic target to inhibit tumor neovascularization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes12010009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823537PMC
December 2020

QSAR Model for Predicting the Cannabinoid Receptor 1 Binding Affinity and Dependence Potential of Synthetic Cannabinoids.

Molecules 2020 Dec 21;25(24). Epub 2020 Dec 21.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.

In recent years, there have been frequent reports on the adverse effects of synthetic cannabinoid (SC) abuse. SCs cause psychoactive effects, similar to those caused by marijuana, by binding and activating cannabinoid receptor 1 (CB1R) in the central nervous system. The aim of this study was to establish a reliable quantitative structure-activity relationship (QSAR) model to correlate the structures and physicochemical properties of various SCs with their CB1R-binding affinities. We prepared tetrahydrocannabinol (THC) and 14 SCs and their derivatives (naphthoylindoles, naphthoylnaphthalenes, benzoylindoles, and cyclohexylphenols) and determined their binding affinity to CB1R, which is known as a dependence-related target. We calculated the molecular descriptors for dataset compounds using an R/CDK (R package integrated with CDK, version 3.5.0) toolkit to build QSAR regression models. These models were established, and statistical evaluations were performed using the mlr and plsr packages in R software. The most reliable QSAR model was obtained from the partial least squares regression method via Y-randomization test and external validation. This model can be applied in vivo to predict the addictive properties of illicit new SCs. Using a limited number of dataset compounds and our own experimental activity data, we built a QSAR model for SCs with good predictability. This QSAR modeling approach provides a novel strategy for establishing an efficient tool to predict the abuse potential of various SCs and to control their illicit use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules25246057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767513PMC
December 2020

Endothelial to Mesenchymal Transition in Pulmonary Vascular Diseases.

Biomedicines 2020 Dec 21;8(12). Epub 2020 Dec 21.

Division of Biological Sciences, Sookmyung Women's University, Seoul 04310, Korea.

Lung diseases, such as pulmonary hypertension and pulmonary fibrosis, are life-threatening diseases and have common features of vascular remodeling. During progression, extracellular matrix protein deposition and dysregulation of proteolytic enzymes occurs, which results in vascular stiffness and dysfunction. Although vasodilators or anti-fibrotic therapy have been mainly used as therapy owing to these characteristics, their effectiveness does not meet expectations. Therefore, a better understanding of the etiology and new therapeutic approaches are needed. Endothelial cells (ECs) line the inner walls of blood vessels and maintain vascular homeostasis by protecting vascular cells from pathological stimuli. Chronic stimulation of ECs by various factors, including pro-inflammatory cytokines and hypoxia, leads to ECs undergoing an imbalance of endothelial homeostasis, which results in endothelial dysfunction and is closely associated with vascular diseases. Emerging studies suggest that endothelial to mesenchymal transition (EndMT) contributes to endothelial dysfunction and plays a key role in the pathogenesis of vascular diseases. EndMT is a process by which ECs lose their markers and show mesenchymal-like morphological changes, and gain mesenchymal cell markers. Despite the efforts to elucidate these molecular mechanisms, the role of EndMT in the pathogenesis of lung disease still requires further investigation. Here, we review the importance of EndMT in the pathogenesis of pulmonary vascular diseases and discuss various signaling pathways and mediators involved in the EndMT process. Furthermore, we will provide insight into the therapeutic potential of targeting EndMT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biomedicines8120639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767472PMC
December 2020

Fast charging with high capacity for aluminum rechargeable batteries using organic additive in an ionic liquid electrolyte.

Phys Chem Chem Phys 2020 Dec;22(47):27525-27528

Materials and Electrochemistry Lab., Department of Chemical Engineering, Inha University, Incheon 22212, Republic of Korea.

Aluminum-ion batteries have many advantages such as the natural abundance of aluminum, high theoretical capacity, and low cost. However, the ionic liquid commonly used as the electrolyte for aluminum-ion batteries has high viscosity, which hinders the migration of charge carriers. In this study, we used various organic solvents as additives for the ionic liquid electrolyte and investigated their effect on the battery performance. The electrolyte containing 45% (v/v) benzene had the best electrochemical properties, which led to a high specific capacity of 90 mA h g-1 at an extremely high current density of 5 A g-1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cp05050dDOI Listing
December 2020

Treatment of purely ligamentous dorsoulnar radiocarpal dislocation with ulnar translation of the carpus: A case report.

Medicine (Baltimore) 2020 Nov;99(48):e23451

Department of Orthopaedic Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Rationale: Radiocarpal fracture-dislocations are extremely infrequent injuries caused by high-energy trauma and involve significant osseous and ligamentous injuries. If not treated properly, it can lead to serious complications such as ulnar translation of the carpus, multidirectional instability, loss of motion, and post-traumatic arthritis. Purely ligamentous injuries are rarer than fracture-dislocation injuries. Because previous studies have reported small patient cohorts, there has been no standardized treatment strategy for purely ligamentous radiocarpal dislocation.

Patient Concerns: A 24-year-old man suffered a left wrist injury in a motorcycle accident. Plain radiographs revealed dorso-ulnar radiocarpal dislocation without radial fracture and Carpal-ulnar distance ratio (CUDR) was 0.16. MRI scans showed the disruption of the dorsal ligaments and capsules and avulsed from the proximal insertion of the volar radiocarpal ligaments.

Diagnosis: Dorsoulnar radiocarpal dislocation with purely ligamentous injury.

Intervention: We removed the interposing chondral fragment from the radiocarpal joint and repaired the radioscaphocapitate (RSC) and radiolunate (RL) ligaments with the Jugger Knot Soft Anchor Suture (Biomet, Inc, Warsaw, IN) and applied additional radiocarpal K-wires and an external fixator to maintain reduction and optimal ligament tension.

Outcomes: The patient showed good clinical results although ulnar translation of the carpus recurred in radiological follow-up.

Lessons: Aggressive surgical management is needed earlier in the treatment of purely ligamentous radiocarpal dislocation, especially if the ulnar translation of the carpus was observed in the initial radiographs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000023451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710183PMC
November 2020

3D Cell Printing of Tissue/Organ-Mimicking Constructs for Therapeutic and Drug Testing Applications.

Int J Mol Sci 2020 Oct 20;21(20). Epub 2020 Oct 20.

Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea.

The development of artificial tissue/organs with the functional maturity of their native equivalents is one of the long-awaited panaceas for the medical and pharmaceutical industries. Advanced 3D cell-printing technology and various functional bioinks are promising technologies in the field of tissue engineering that have enabled the fabrication of complex 3D living tissue/organs. Various requirements for these tissues, including a complex and large-volume structure, tissue-specific microenvironments, and functional vasculatures, have been addressed to develop engineered tissue/organs with native relevance. Functional tissue/organ constructs have been developed that satisfy such criteria and may facilitate both in vivo replenishment of damaged tissue and the development of reliable in vitro testing platforms for drug development. This review describes key developments in technologies and materials for engineering 3D cell-printed constructs for therapeutic and drug testing applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21207757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589604PMC
October 2020

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

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

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

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

Download full-text PDF

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

Crystal structure of the HMG domain of human BAF57 and its interaction with four-way junction DNA.

Biochem Biophys Res Commun 2020 12 30;533(4):919-924. Epub 2020 Sep 30.

Structural Biochemistry & Molecular Biophysics Laboratory, Department of Biochemistry, College of Life Sciences & Biotechnology, Yonsei University, Seoul, 120-749, South Korea. Electronic address:

The SWI/SNF chromatin remodeling complex plays important roles in gene regulation and it is classified as the SWI/SNF complex in yeast and BAF complex in vertebrates. BAF57, one of the subunits that forms the chromatin remodeling complex core, is well conserved in the BAF complex of vertebrates, which is replaced by bap111 in the Drosophila BAP complex and does not have a counterpart in the yeast SWI/SNF complex. This suggests that BAF57 is a key component of the chromatin remodeling complex in higher eukaryotes. BAF57 contains a HMG domain, which is widely distributed among various proteins and functions as a DNA binding motif. Most proteins with HMG domain bind to four-way junction (4WJ) DNA. Here, we report the crystal structure of the HMG domain of BAF57 (BAF57) at a resolution of 2.55 Å. The structure consists of three α-helices and adopts an L-shaped form. The overall structure is stabilized by a hydrophobic core, which is formed by hydrophobic residues. The binding affinity between BAF57 and 4WJ DNA is determined as a 295.83 ± 1.05 nM using a fluorescence quenching assay, and the structure revealed 4WJ DNA binding site of BAF57. Our data will serve structural basis in understanding the roles of BAF57 during chromatin remodeling process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2020.09.094DOI Listing
December 2020

Hybridisation of perovskite nanocrystals with organic molecules for highly efficient liquid scintillators.

Light Sci Appl 2020 7;9:156. Epub 2020 Sep 7.

Division of Physics and Semiconductor Science, Dongguk University, Seoul, 04620 Republic of Korea.

Compared with solid scintillators, liquid scintillators have limited capability in dosimetry and radiography due to their relatively low light yields. Here, we report a new generation of highly efficient and low-cost liquid scintillators constructed by surface hybridisation of colloidal metal halide perovskite CsPbA (A: Cl, Br, I) nanocrystals (NCs) with organic molecules (2,5-diphenyloxazole). The hybrid liquid scintillators, compared to state-of-the-art CsI and GdOS, demonstrate markedly highly competitive radioluminescence quantum yields under X-ray irradiation typically employed in diagnosis and treatment. Experimental and theoretical analyses suggest that the enhanced quantum yield is associated with X-ray photon-induced charge transfer from the organic molecules to the NCs. High-resolution X-ray imaging is demonstrated using a hybrid CsPbBr NC-based liquid scintillator. The novel X-ray scintillation mechanism in our hybrid scintillators could be extended to enhance the quantum yield of various types of scintillators, enabling low-dose radiation detection in various fields, including fundamental science and imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41377-020-00391-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477552PMC
September 2020

3D printing of drug-loaded multi-shell rods for local delivery of bevacizumab and dexamethasone: A synergetic therapy for retinal vascular diseases.

Acta Biomater 2020 10 11;116:174-185. Epub 2020 Sep 11.

School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, South Korea; Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, South Korea. Electronic address:

The clinical therapy for retinal vascular diseases requires repeated intravitreal injections of drugs owing to their short half-life, which imposes health and economic burdens on patients. Therefore, it is necessary to develop an advanced drug delivery system that can prolong the drug activity and minimize secondary complications. In this study, we developed a core/shell drug-loaded rod (drug rod) to deliver two types of drugs (bevacizumab (BEV) and dexamethasone (DEX)) from a single implant. The coaxial printing technique allowed BEV and DEX to be released with different kinetics at the same site by using a polymeric shell and a hydrogel core, respectively. The suggested printing technique facilitates the production of drug rods with various dimensions and drug concentrations, and the multi-layered design allows to adjust the release profile of dual drug-delivery system. The rod was injected in rat vitreous less invasively using a small-gauge needle. Further, we validated the efficacy of the implanted drug rods in inhibiting inflammatory responses and long-term suppression of neovascularization compared to the conventional intravitreal injection of BEV in animal model, indicating that the drug rods can be an alternative therapeutic approach for the treatment of various types of retinal vascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2020.09.015DOI Listing
October 2020

Internal Fixation of Pauwels Type-3 Undisplaced-incomplete Insufficiency Femoral Neck Fractures with Cephalomedullary Nails.

Hip Pelvis 2020 Jun 15;32(2):105-111. Epub 2020 Jun 15.

Department of Orthopedic Surgery, The Catholic University of Korea, St. Vincent Hospital, Suwon, Korea.

Femoral neck stress fractures are rare and when treating are difficult to achieve favorable outcomes. This study characterizes outcomes associated with the use of cephalomedullary nails for fixation of Pauwels type-3 vertical femoral neck undisplaced-incomplete insufficiency fractures. Four consecutive patients with a Pauwels type-3 vertical femoral neck tensile insufficiency fracture from 2016 to 2018 were reviewed. Magnetic resonance imaging data revealed tensile visible fracture lines and hip-joint effusions with a high shear angle. For all patients, bone mineral density and vitamin D levels were low; vitamin D therapy was initiated immediately. Surgical procedures were conducted with cephalomedullary nails (Gamma 3 locking nail system; Stryker) under general anesthesia. A cephalomedullary nail appears to be a safe and effective alternative to the use of multiple parallel screws or a sliding hip screw for fixation of vertical femoral neck stress fractures (level of evidence: Level V).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5371/hp.2020.32.2.105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295618PMC
June 2020

Angiogenesis and vasculogenic mimicry as therapeutic targets in ovarian cancer.

BMB Rep 2020 Jun;53(6):291-298

Division of Biological Sciences, Sookmyung Women's University, Seoul 04310; Research Institute for Women's Health, Sookmyung Women's University, Seoul 04310, Korea.

Tumor angiogenesis is an essential process for growth and metastasis of cancer cells as it supplies tumors with oxygen and nutrients. During tumor angiogenesis, many pro-angiogenic factors are secreted by tumor cells to induce their own vascularization via activation of pre-existing host endothelium. However, accumulating evidence suggests that vasculogenic mimicry (VM) is a key alternative mechanism for tumor vascularization when tumors are faced with insufficient supply of oxygen and nutrients. VM is a tumor vascularization mechanism in which tumors create a blood supply system, in contrast to tumor angiogenesis mechanisms that depend on pre-existing host endothelium. VM is closely associated with tumor progression and poor prognosis in many cancers. Therefore, inhibition of VM may be a promising therapeutic strategy and may overcome the limitations of anti-angiogenesis therapy for cancer patients. In this review, we provide an overview of the current anti-angiogenic therapies for ovarian cancer and the current state of knowledge regarding the links between microRNAs and the VM process, with a focus on the mechanism that regulates associated signaling pathways in ovarian cancer. Moreover, we discuss the potential for VM as a therapeutic strategy against ovarian cancer. [BMB Reports 2020; 53(6): 291-298].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330806PMC
June 2020

New Surface Modification Method To Develop a PET-Based Membrane with Enhanced Ion Permeability and Organic Fouling Resistance for Efficient Production of Marine Microalgae.

ACS Appl Mater Interfaces 2020 Jun 19;12(22):25253-25265. Epub 2020 May 19.

Department of Polymer Science and Engineering, Inha University, Incheon 22212, Republic of Korea.

This paper presents a new surface modification strategy to develop a poly(ethylene terephthalate) (PET)-based membrane having a hydrophilic surface, high nutrient ion permeability, sufficient mechanical strength, and organic fouling resistance, using an anthracene (ANT)-attached polyethylene glycol (PEG) surface modification agent (SMA) synthesized in this work. During the modification process, the ANT parts of the SMAs poke through and anchor to the surface of a commercial PET woven fabric via physical interactions and mechanical locking. The PEG chain parts coat the surface in the brush and arch forms, which generates a hydration layer on the fabric surface. The consequently obtained surface property and unique structure of the modified PET-based membrane result in higher nitrate ion permeability, organic fouling resistance, and microalgae production compared to those of the unmodified one. These are also affected by the molecular weight of the PEG and the number density of the anchored SMAs. The study demonstrates that this new surface modification method has the potential to allow the development of a desirable PET-based membrane for the efficient massive production of marine microalgae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c00546DOI Listing
June 2020

Ginsenoside Rg3 protects against iE-DAP-induced endothelial-to-mesenchymal transition by regulating the miR-139-5p-NF-κB axis.

J Ginseng Res 2020 Mar 21;44(2):300-307. Epub 2019 Jan 21.

Department of Life Systems, Sookmyung Women's University, Seoul, Republic of Korea.

Background: Emerging evidence suggests that endothelial-to-mesenchymal transition (EndMT) in endothelial dysfunction due to persistent inflammation is a key component and emerging concept in the pathogenesis of vascular diseases. Ginsenoside Rg3 (Rg3), an active compound from red ginseng, has been known to be important for vascular homeostasis. However, the effect of Rg3 on inflammation-induced EndMT has never been reported. Here, we hypothesize that Rg3 might reverse the inflammation-induced EndMT and serve as a novel therapeutic strategy for vascular diseases.

Methods: EndMT was examined under an inflammatory condition mediated by the NOD1 agonist, γ-d-glutamyl-meso-diaminopimelic acid (iE-DAP), treatment in human umbilical vein endothelial cells. The expression of EndMT markers was determined by Western blot analysis, real-time polymerase chain reaction, and immunocytochemistry. The underlying mechanisms of Rg3-mediated EndMT regulation were investigated by modulating the microRNA expression.

Results: The NOD1 agonist, iE-DAP, led to a fibroblast-like morphology change with a decrease in the expression of endothelial markers and an increase in the expression of the mesenchymal marker, namely EndMT. On the other hand, Rg3 markedly attenuated the iE-DAP-induced EndMT and preserved the endothelial phenotype. Mechanically, miR-139 was downregulated in cells with iE-DAP-induced EndMT and partly reversed in response to Rg3 via the regulation of NF-κB signaling, suggesting that the Rg3-miR-139-5p-NF-κB axis is a key mediator in iE-DAP-induced EndMT.

Conclusion: These results suggest, for the first time, that Rg3 can be used to inhibit inflammation-induced EndMT and may be a novel therapeutic option against EndMT-associated vascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgr.2019.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031736PMC
March 2020

Selective retina therapy monitoring by speckle variance optical coherence tomography for dosimetry control.

J Biomed Opt 2020 02;25(2):1-9

Johns Hopkins Univ., United States.

Significance: Selective retina therapy (SRT) selectively targets the retinal pigment epithelium (RPE) and reduces negative side effects by avoiding thermal damages of the adjacent photoreceptors, the neural retina, and the choroid. However, the selection of proper laser energy for the SRT is challenging because of ophthalmoscopically invisible lesions in the RPE and different melanin concentrations among patients or even regions within an eye.

Aim: We propose and demonstrate SRT monitoring based on speckle variance optical coherence tomography (svOCT) for dosimetry control.

Approach: M-scans, time-resolved sequence of A-scans, of ex vivo bovine retina irradiated by 1.7-μs duration laser pulses were obtained by a swept-source OCT. SvOCT images were calculated as interframe intensity variance of the sequence. Spatial and temporal temperature distributions in the retina were numerically calculated in a 2-D retinal model using COMSOL Multiphysics. Microscopic images of treated spots were obtained before and after removing the upper neural retinal layer to assess the damage in both RPE and neural layers.

Results: SvOCT images show abrupt speckle variance changes when the retina is irradiated by laser pulses. The svOCT intensities averaged in RPE and photoreceptor layers along the axial direction show sharp peaks corresponding to each laser pulse, and the peak values were proportional to the laser pulse energy. The calculated temperatures in the neural retina layer and RPE were linearly fitted to the svOCT peak values, and the temperature of each lesion was estimated based on the fitting. The estimated temperatures matched well with previously reported results.

Conclusion: We found a reliable correlation between the svOCT peak values and the degree of retinal lesion formation, which can be used for selecting proper laser energy during SRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1117/1.JBO.25.2.026001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019183PMC
February 2020

RNA nanotechnology in synthetic biology.

Curr Opin Biotechnol 2020 06 5;63:135-141. Epub 2020 Feb 5.

Mechanical and Aerospace Engineering, University of California at Los Angeles, 420 Westwood Plaza, Los Angeles, CA 90095, United States. Electronic address:

We review recent advances in the design and expression of synthetic RNA sequences inside cells, to regulate gene expression and to achieve spatial localization of components. We focus on approaches that exploit the programmability of the secondary and tertiary structure of RNA to build scalable and modular devices that fold spontaneously and have the capacity to respond to environmental inputs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.copbio.2019.12.016DOI Listing
June 2020

Effects of Femur Position on Radiographic Assessment of Femoral Head and Neck Excision Completeness in Cats.

Vet Comp Orthop Traumatol 2020 Mar 30;33(2):130-136. Epub 2020 Jan 30.

West Coast Specialty and Emergency Animal Hospital, Fountain Valley, California, United States.

Objective:  The aim of this study was to determine the effect of femoral position on radiographic assessment of completeness of femoral head and neck excision (FHNE) in cats.

Study Design:  The study included 20 femurs from adult cats. Complete FHNE was performed on 10 femurs and incomplete excision consisting of inadequate excision of the distal medial femoral neck was performed on 10 femurs. The lesser trochanter was maintained in all femurs. Each femur was positioned through a predetermined set of eight radiographic views about the long axis. Sensitivity (SE), specificity (SP) and accuracy were calculated for each femoral position.

Results:  Craniocaudal views of the femur in external rotation (30° and 45°) had the highest SE, SP and accuracy (SE: 97.5% and 97.5%; SP: 92.5% and 95%; and accuracy: 95% and 96%, respectively) followed by external rotation of 15 (SE: 92.5%, SP: 87.5% and accuracy: 90%) relative to standard craniocaudal (SE: 57.5%, SP: 72.5%, accuracy: 65%) and lateromedial (SE: 2.5%, SP: 0%, accuracy: 1%) radiographic views.

Conclusions:  Evaluation of craniocaudal radiographic views with the femurs in external rotation can increase the ability to assess the adequacy of the FHNE in cats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0039-3400485DOI Listing
March 2020

The CBX family of proteins in transcriptional repression and memory.

J Biosci 2020 ;45

Department of Molecular Biology and MGH Research Institute, Massachusetts General Hospital, Boston, MA, USA.

For mammals to develop properly, master regulatory genes must be repressed appropriately in a heritable manner. This review concerns the Polycomb Repressive Complex 1 (PRC1) family and the relationship between the establishment of repression and memory of the repressed state. The primary focus is on the CBX family of proteins in PRC1 complexes and their role in both chromatin compaction and phase separation. These two activities are linked and might contribute to both repression and memory.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2020

De novo-designed translation-repressing riboregulators for multi-input cellular logic.

Nat Chem Biol 2019 12 4;15(12):1173-1182. Epub 2019 Nov 4.

Biodesign Center for Molecular Design and Biomimetics, The Biodesign Institute, Arizona State University, Tempe, AZ, USA.

Efforts to construct synthetic biological circuits with more complex functions have often been hindered by the idiosyncratic behavior, limited dynamic range and crosstalk of commonly utilized parts. Here, we employ de novo RNA design to develop two high-performance translational repressors with sensing and logic capabilities. These synthetic riboregulators, termed toehold repressors and three-way junction (3WJ) repressors, detect transcripts with nearly arbitrary sequences, repress gene expression by up to 300-fold and yield orthogonal sets of up to 15 devices. Automated forward engineering is used to improve toehold repressor dynamic range and SHAPE-Seq is applied to confirm the designed switching mechanism of 3WJ repressors in living cells. We integrate the modular repressors into biological circuits that execute universal NAND and NOR logic and evaluate the four-input expression NOT ((A1 AND A2) OR (B1 AND B2)) in Escherichia coli. These capabilities make toehold and 3WJ repressors valuable new tools for biotechnological applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41589-019-0388-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864284PMC
December 2019

Programmable CRISPR-Cas Repression, Activation, and Computation with Sequence-Independent Targets and Triggers.

ACS Synth Biol 2019 07 10;8(7):1583-1589. Epub 2019 Jul 10.

Wyss Institute for Biologically Inspired Engineering , Harvard University , Boston , Massachusetts 02115 , United States.

The programmability of CRISPR-derived Cas9 as a sequence-specific DNA-targeting protein has made it a powerful tool for genomic manipulation in biological research and translational applications. Cas9 activity can be programmably engineered to respond to nucleic acids, but these efforts have focused primarily on single-input control of Cas9, and until recently, they were limited by sequence dependence between parts of the guide RNA and the sequence to be detected. Here, we not only design and present DNA- and RNA-sensing conditional guide RNA (cgRNA) that have no such sequence constraints, but also demonstrate a complete set of logical computations using these designs on DNA and RNA sequence inputs, including AND, OR, NAND, and NOR. The development of sequence-independent nucleic acid-sensing CRISPR-Cas9 systems with multi-input logic computation capabilities could lead to improved genome engineering and regulation as well as the construction of synthetic circuits with broader functionality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acssynbio.9b00141DOI Listing
July 2019