Publications by authors named "Sang Jin Lee"

464 Publications

Ultrafast coherent motion and helix rearrangement of homodimeric hemoglobin visualized with femtosecond X-ray solution scattering.

Nat Commun 2021 06 16;12(1):3677. Epub 2021 Jun 16.

Department of Chemistry and KI for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.

Ultrafast motion of molecules, particularly the coherent motion, has been intensively investigated as a key factor guiding the reaction pathways. Recently, X-ray free-electron lasers (XFELs) have been utilized to elucidate the ultrafast motion of molecules. However, the studies on proteins using XFELs have been typically limited to the crystalline phase, and proteins in solution have rarely been investigated. Here we applied femtosecond time-resolved X-ray solution scattering (fs-TRXSS) and a structure refinement method to visualize the ultrafast motion of a protein. We succeeded in revealing detailed ultrafast structural changes of homodimeric hemoglobin involving the coherent motion. In addition to the motion of the protein itself, the time-dependent change of electron density of the hydration shell was tracked. Besides, the analysis on the fs-TRXSS data of myoglobin allows for observing the effect of the oligomeric state on the ultrafast coherent motion.
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http://dx.doi.org/10.1038/s41467-021-23947-7DOI Listing
June 2021

Bio-plotted hydrogel scaffold with core and sheath strand-enhancing mechanical and biological properties for tissue regeneration.

Colloids Surf B Biointerfaces 2021 Jun 10;205:111919. Epub 2021 Jun 10.

Department of Nature-Inspired System and Application, Korea Institute of Machinery and Materials (KIMM), Daejeon, 34103, Republic of Korea. Electronic address:

Three-dimensional bio-plotted scaffolds constructed from encapsulated biomaterials or so-called "bio-inks" have received much attention for tissue regeneration applications, as advances in this technology have enabled more precise control over the scaffold structure. As a base material of bio-ink, sodium alginate (SA) has been used extensively because it provides suitable biocompatibility and printability in terms of creating a biomimetic environment for cell growth, even though it has limited cell-binding moiety and relatively weak mechanical properties. To improve the mechanical and biological properties of SA, herein, we introduce a strategy using hydroxyapatite (HA) nanoparticles and a core/sheath plotting (CSP) process. By characterizing the rheological and chemical properties and printability of SA and SA/HA-blended inks, we successfully fabricated bio-scaffolds using CSP. In particular, the mechanical properties of the scaffold were enhanced with increasing concentrations of HA particles and SA hydrogel. Specifically, HA particles blended with the SA hydrogel of core strands enhanced the biological properties of the scaffold by supporting the sheath part of the strand encapsulating osteoblast-like cells. Based on these results, the proposed scaffold design shows great promise for bone-tissue regeneration and engineering applications.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111919DOI Listing
June 2021

Direct Injection of Hydrogels Embedding Gold Nanoparticles for Local Therapy after Spinal Cord Injury.

Biomacromolecules 2021 Jun 7. Epub 2021 Jun 7.

Department of Neurosurgery, CHA Bundang Medical Center, CHA University, 59, Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13496, Republic of Korea.

In this study, we created a hydrogel composed of glycol chitosan (gC) and oxidized hyaluronate (oHA). Gold nanoparticles (GNPs) were conjugated with ursodeoxycholic acid (UDCA). The GNP-UDCA complex was embedded into gC-oHA (CHA) hydrogels to form a CHA-GNP-UDCA gel. This CHA-GNP-UDCA gel was injected once into an epicenter of an injured region in SCI rats. Near-infrared (NIR) irradiation was then applied to the lesion as a means of local therapy. To optimize the viscosity for injection into a lesion, several volume ratios of gC and oHA were investigated using scanning electron microscopy and a rotating rheometer. The optimally synthesized CHA-GNP-UDCA gel under NIR irradiation suppressed the production of inflammatory cytokines in vitro. In addition, the optimized CHA-GNP-UDCA gel under NIR irradiation inhibited the cystic cavity of the lesion and significantly improved the hindlimb function. The production of inflammatory cytokines following SCI was significantly inhibited in the CHA-GNP-UDCA gel + NIR group. CHA-GNP-UDCA gels with NIR irradiation can therefore have therapeutic effects for those with spinal cord injuries.
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http://dx.doi.org/10.1021/acs.biomac.1c00281DOI Listing
June 2021

Self-aligned myofibers in 3D bioprinted extracellular matrix-based construct accelerate skeletal muscle function restoration.

Appl Phys Rev 2021 Jun;8(2):021405

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.

To achieve rapid skeletal muscle function restoration, many attempts have been made to bioengineer functional muscle constructs by employing physical, biochemical, or biological cues. Here, we develop a self-aligned skeletal muscle construct by printing a photo-crosslinkable skeletal muscle extracellular matrix-derived bioink together with poly(vinyl alcohol) that contains human muscle progenitor cells. To induce the self-alignment of human muscle progenitor cells, uniaxially aligned micro-topographical structure in the printed constructs is created by a fibrillation/leaching of poly(vinyl alcohol) after the printing process. The results demonstrate that the synergistic effect of tissue-specific biochemical signals (obtained from the skeletal muscle extracellular matrix-derived bioink) and topographical cues [obtained from the poly(vinyl alcohol) fibrillation] improves the myogenic differentiation of the printed human muscle progenitor cells with cellular alignment. Moreover, this self-aligned muscle construct shows the accelerated integration with neural networks and vascular ingrowth , resulting in rapid restoration of muscle function. We demonstrate that combined biochemical and topographic cues on the 3D bioprinted skeletal muscle constructs can effectively reconstruct the extensive muscle defect injuries.
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http://dx.doi.org/10.1063/5.0039639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117312PMC
June 2021

Non-invasive in vivo monitoring of transplanted stem cells in 3D-bioprinted constructs using near-infrared fluorescent imaging.

Bioeng Transl Med 2021 May 26;6(2):e10216. Epub 2021 Mar 26.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard Winston-Salem North Carolina USA.

Cell-based tissue engineering strategies have been widely established. However, the contributions of the transplanted cells within the tissue-engineered scaffolds to the process of tissue regeneration remain poorly understood. Near-infrared (NIR) fluorescence imaging systems have great potential to non-invasively monitor the transplanted cell-based tissue constructs. In this study, labeling mesenchymal stem cells (MSCs) using a lipophilic pentamethine indocyanine (CTNF127, emission at 700 nm) as a NIR fluorophore was optimized, and the CTNF127-labeled MSCs (NIR-MSCs) were printed embedding in gelatin methacryloyl bioink. The NIR-MSCs-loaded bioink showed excellent printability. In addition, NIR-MSCs in the 3D constructs showed high cell viability and signal stability for an extended period in vitro. Finally, we were able to non-invasively monitor the NIR-MSCs in constructs after implantation in a rat calvarial bone defect model, and the transplanted cells contributed to tissue formation without specific staining. This NIR-based imaging system for non-invasive cell monitoring in vivo could play an active role in validating the cell fate in cell-based tissue engineering applications.
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http://dx.doi.org/10.1002/btm2.10216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126817PMC
May 2021

Anterior cruciate ligament avulsion fracture following medial unicompartmental knee arthroplasty: A case report.

Authors:
Sang Jin Lee

Ann Med Surg (Lond) 2021 May 19;65:102328. Epub 2021 Apr 19.

Department of Orthopedic Surgery, Haeundae Paik Hospital, Inje University, Busan, South Korea.

Introduction: Anterior cruciate ligament (ACL) avulsion fracture after unicompartmental knee arthroplasty (UKA) has not been reported until recently. We describe a case of ACL avulsion fracture that developed after medial UKA.

Case Presentation: A 57-year-old woman underwent UKA for right medial compartment osteoarthritis. She developed knee pain and swelling at 2 weeks after UKA, and radiographs showed an ACL avulsion fracture at 3 weeks after UKA. After conservative treatment failed, the fracture was fixed using screws. After 5 months from internal fixation, bone union was confirmed, and the screws were removed. At 16 months after removing screws, there was no further complication.

Discussion: The patient did not exhibit a fracture on the radiograph taken immediately after UKA. We carefully re-examined the radiographs and observed a 5-mm horizontal cement shadow on the lateral side of the tibial component. It is thought that excessive lateral resection of the proximal tibia during UKA may have resulted in a micro fracture and this outcome. In the present case, the posterior slope angle of the tibial component measured postoperatively was 11.5 degrees. The angle of more than 7 degrees along with excessive horizontal resection of the proximal tibia probably increased load on the ACL.

Conclusion: If patients exhibit a horizontal cement shadow near the tibial component and a higher posterior slope angle of the tibial component on the radiograph after UKA, surgeons should be aware of possible ACL avulsion fracture and perform additional radiological examinations in patients with continuous knee pain and swelling.
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http://dx.doi.org/10.1016/j.amsu.2021.102328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099496PMC
May 2021

Cell-Laden Multiple-Step and Reversible 4D Hydrogel Actuators to Mimic Dynamic Tissue Morphogenesis.

Adv Sci (Weinh) 2021 05 1;8(9):2004616. Epub 2021 Mar 1.

Department of Biomedical Engineering Case Western Reserve University 10900 Euclid Avenue Cleveland OH 44106 USA.

Shape-morphing hydrogels bear promising prospects as soft actuators and for robotics. However, they are mostly restricted to applications in the abiotic domain due to the harsh physicochemical conditions typically necessary to induce shape morphing. Here, multilayer hydrogel actuator systems are developed using biocompatible and photocrosslinkable oxidized, methacrylated alginate and methacrylated gelatin that permit encapsulation and maintenance of living cells within the hydrogel actuators and implement programmed and controlled actuations with multiple shape changes. The hydrogel actuators encapsulating cells enable defined self-folding and/or user-regulated, on-demand-folding into specific 3D architectures under physiological conditions, with the capability to partially bioemulate complex developmental processes such as branching morphogenesis. The hydrogel actuator systems can be utilized as novel platforms for investigating the effect of programmed multiple-step and reversible shape morphing on cellular behaviors in 3D extracellular matrix and the role of recapitulating developmental and healing morphogenic processes on promoting new complex tissue formation.
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http://dx.doi.org/10.1002/advs.202004616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097354PMC
May 2021

Combinations of photoinitiator and UV absorber for cell-based digital light processing (DLP) bioprinting.

Biofabrication 2021 May 24;13(3). Epub 2021 May 24.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States of America.

Digital light processing (DLP) bioprinting, which provides predominant speed, resolution, and adaptability for fabricating complex cell-laden three-dimensional (3D) structures, requires a combination of photoinitiator (PI) and UV absorber (UA) that plays critical roles during the photo-polymerization of bioinks. However, the PI and UA combination has not been highlighted for cell-based DLP bioprinting. In this study, the most used PIs and UAs in cell-based bioprinting were compared to optimize a combination that can ensure the maximum DLP printability, while maintaining the cellular activities during the process. The crosslinking time and printability of PIs were assessed, which are critical in minimizing the cell damage by the UV exposure during the fabrication process. On the other hand, the UAs were evaluated based on their ability to prevent the over-curing of layers beyond the focal layer and the scattering of light, which are required for the desirable crosslinking of a hydrogel and high resolution (25-50ms) to create a complex 3D cell-laden construct. Lastly, the cytotoxicity of PIs and UAs was assessed by measuring the cellular activity of 2D cultured and 3D bioprinted cells. The optimized PI and UA combination provided high initial cell viability (>90%) for up to 14 days in culture and could fabricate complex 3D structures like a perfusable heart-shaped construct with open vesicles and atriums. This combination can provide a potential starting condition when preparing the bioink for the cell-based DLP bioprinting in tissue engineering applications.
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http://dx.doi.org/10.1088/1758-5090/abfd7aDOI Listing
May 2021

Dynamic Changes in Fecal Microbial Communities of Neonatal Dairy Calves by Aging and Diarrhea.

Animals (Basel) 2021 Apr 13;11(4). Epub 2021 Apr 13.

Department of Animal Science, College of Natural Resources & Life Science, Pusan National University, Miryang 50463, Korea.

Microbiota plays a critical role in the overall growth performance and health status of dairy cows, especially during their early life. Several studies have reported that fecal microbiome of neonatal calves is shifted by various factors such as diarrhea, antibiotic treatment, or environmental changes. Despite the importance of gut microbiome, a lack of knowledge regarding the composition and functions of microbiota impedes the development of new strategies for improving growth performance and disease resistance during the neonatal calf period. In this study, we utilized next-generation sequencing to monitor the time-dependent dynamics of the gut microbiota of dairy calves before weaning (1-8 weeks of age) and further investigated the microbiome changes caused by diarrhea. Metagenomic analysis revealed that continuous changes, including increasing gut microbiome diversity, occurred from 1 to 5 weeks of age. However, the composition and diversity of the fecal microbiome did not change after 6 weeks of age. The most prominent changes in the fecal microbiome composition caused by aging at family level were a decreased abundance of and and an increased abundance of . Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis indicated that the abundance of microbial genes associated with various metabolic pathways changed with aging. All calves with diarrhea symptoms showed drastic microbiome changes and about a week later returned to the microbiome of pre-diarrheal stage regardless of age. At phylum level, abundance of Bacteroidetes was decreased ( and that of Proteobacteria increased ( = 0.07) during diarrhea. PICRUSt analysis indicated that microbial metabolism-related genes, such as starch and sucrose metabolism, sphingolipid metabolism, alanine aspartate, and glutamate metabolism were significantly altered in diarrheal calves. Together, these results highlight the important implications of gut microbiota in gut metabolism and health status of neonatal dairy calves.
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http://dx.doi.org/10.3390/ani11041113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070554PMC
April 2021

Contribution of a distal radioulnar joint stabilizer on forearm stability: A modeling study.

Proc Inst Mech Eng H 2021 Jul 21;235(7):819-826. Epub 2021 Apr 21.

Department of Mechanical Engineering, Kyung Hee University, Yongin, Korea.

Instability of the forearm is a complex problem that leads to pain and limited motions. Up to this time, no universal consensus has yet been reached as regards the optimal treatment for forearm instability. In some cases, conservative treatments are recommended for forearm instability injuries. However, quantitative studies on the conservative treatment of forearm instability are lacking. The present study developed a finite element model of the forearm to investigate the contribution of the distal radioulnar joint stabilizer on forearm stability. The stabilizer was designed to provide stability between the radius and ulna. The forearm model with and without the stabilizer was tested using the pure transverse separation and radial pull test for the different ligament sectioned models. The percentage contribution of the stabilizer and ligament structures resisting the load on the forearm was estimated. For the transverse stability of the forearm, the central band resisted approximately 50% of the total transverse load. In the longitudinal instability, the interosseous membrane resisted approximately 70% of the axial load. With the stabilizer, models showed that the stabilizer provided the transverse stability and resisted almost 1/4 of the total transverse load in the ligament sectioned models. The stabilizer provided transverse stability and reduced the loading on the ligaments. We suggested that a stabilizer can be applied in the conservative management of patients who do not have the gross longitudinal instability with the interosseous membrane and the triangular fibrocartilage complex disruption.
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http://dx.doi.org/10.1177/09544119211011334DOI Listing
July 2021

Changes in Blood Metabolites and Immune Cells in Holstein and Jersey Dairy Cows by Heat Stress.

Animals (Basel) 2021 Mar 31;11(4). Epub 2021 Mar 31.

Dairy Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Korea.

Owing to increasing global temperatures, heat stress is a major problem affecting dairy cows, and abnormal metabolic responses during heat stress likely influence dairy cow immunity. However, the mechanism of this crosstalk between metabolism and immunity during heat stress remains unclear. We used two representative dairy cow breeds, Holstein and Jersey, with distinct heat-resistance characteristics. To understand metabolic and immune responses to seasonal changes, normal environmental and high-heat environmental conditions, we assessed blood metabolites and immune cell populations. In biochemistry analysis from sera, we found that variety blood metabolites were decreased in both Holstein and Jersey cows by heat stress. We assessed changes in immune cell populations in peripheral blood mononuclear cells (PBMCs) using flow cytometry. There were breed-specific differences in immune-cell population changes. Heat stress only increased the proportion of B cells (CD4-CD21+) and heat stress tended to decrease the proportion of monocytes (CD11b+CD172a+) in Holstein cows. Our findings expand the understanding of the common and specific changes in metabolism and immune response of two dairy cow breeds under heat stress conditions.
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http://dx.doi.org/10.3390/ani11040974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065422PMC
March 2021

BST204 Protects Dexamethasone-Induced Myotube Atrophy through the Upregulation of Myotube Formation and Mitochondrial Function.

Int J Environ Res Public Health 2021 03 1;18(5). Epub 2021 Mar 1.

Research Institute of Pharmaceutical Science, College of Pharmacy, Sookmyung Women's University, Seoul 04310, Korea.

BST204 is a purified ginseng dry extract that has an inhibitory effect on lipopolysaccharide-induced inflammatory responses, but its effect on muscle atrophy is yet to be investigated. In this study, C2C12 myoblasts were induced to differentiate for three days followed by the treatment of dexamethasone (DEX), a corticosteroid drug, with vehicle or BST204 for one day and subjected to immunoblotting, immunocytochemistry, qRT-PCR and biochemical analysis for mitochondrial function. BST204 alleviates the myotube atrophic effect mediated by DEX via the activation of protein kinase B/mammalian target of rapamycin (Akt/mTOR) signaling. Through this pathway, BST204 suppresses the expression of muscle-specific E3 ubiquitin ligases contributing to the enhanced myotube formation and enlarged myotube diameter in DEX-treated myotubes. In addition, BST204 treatment significantly decreases the mitochondrial reactive oxygen species production in DEX-treated myotubes. Furthermore, BST204 improves mitochondrial function by upregulating the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) in DEX-induced myotube atrophy. This study provides a mechanistic insight into the effect of BST204 on DEX-induced myotube atrophy, suggesting that BST204 has protective effects against the toxicity of a corticosteroid drug in muscle and promising potential as a nutraceutical remedy for the treatment of muscle weakness and atrophy.
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http://dx.doi.org/10.3390/ijerph18052367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957540PMC
March 2021

Role of RGMc as a Neogenin Ligand in Follicular Development in the Ovary.

Biomedicines 2021 Mar 10;9(3). Epub 2021 Mar 10.

CHA Fertility Center Seoul Station, Seoul 04637, Korea.

There is currently no cure for infertility in women with a poor ovarian response (POR). Neogenin is reported to be abundantly expressed in the ovary; however, its role in mammalian follicular development is unclear and its ligand and signaling pathway remain uncertain. We systematically investigated the role of neogenin and the ligand repulsive guidance molecule c (RGMc) during follicular development. We treated hyperstimulated mouse ovaries with RGMc and analyzed follicular development. Furthermore, we investigated clusters of up/downregulated genes in RGMc-treated ovaries using whole-transcriptome next-generation sequencing (NGS). In addition, we investigated whether expression of up/downregulated factors identified by NGS was also altered in cumulus cells (CCs) of patients with a POR. The number of oocytes was 40% higher in RGMc-treated ovaries than in control ovaries. NGS data indicated that prostaglandin D2 (PGD2) was involved in the RGMc signaling pathway during follicular development. RGMc treatment significantly elevated the PGD2 level in culture medium of CCs obtained from patients with a POR. Our results demonstrate that RGMc as neogenin ligand promotes follicular development in ovaries via the PGD2 signaling pathway. Therefore, it may be possible to use RGMc for ovarian stimulation in patients with a POR.
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http://dx.doi.org/10.3390/biomedicines9030280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999520PMC
March 2021

Record of North American boreal forest fires in northwest Greenland snow.

Chemosphere 2021 Aug 6;276:130187. Epub 2021 Mar 6.

Analysis Service Center, Diatech Korea Co., Ltd., Seoul, 05808, Republic of Korea.

We present boreal forest fire proxies in a northwest Greenland snowpit spanning a period of six years, from spring 2003 to summer 2009. Levoglucosan (CHO) is a specific organic molecular marker of biomass burning caused by boreal forest fires. In this study, levoglucosan was determined via liquid chromatography/negative ion electrospray ionization-tandem mass spectrometry, wherein isotope-dilution and multiple reaction monitoring methods are employed. Ammonium (NH) and oxalate (CO), traditional biomass burning proxies, were determined using two-channel ion chromatography. In the northwest Greenland snowpit, peaks in levoglucosan, ammonium, and oxalate were observed in snow layers corresponding to the summer-fall seasons of 2004 and 2005. Considered together, these spikes are a marker for large boreal forest fires. The levoglucosan deposited in the Greenland snow was strongly dependent on long-range atmospheric transportation. A 10-day backward air mass trajectory analysis supports that the major contributors were air masses from North America. In addition, satellite-derived carbon monoxide (CO) and ammonia (NH) concentrations suggest that chemicals from North American boreal forest fires during the summer-fall of 2004 and 2005 were transported to Greenland. However, large boreal fires in Siberia in 2003 and 2008 were not recorded in the snowpit. The sub-annual resolution measurements of levoglucosan and ammonium can distinguish between the contributions of past boreal forest fires and soil emissions from anthropogenic activity to Greenland snow and ice.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130187DOI Listing
August 2021

Thermal Characteristics of Cu Matrix-SiC Filler Composite Using Nano-Sized Cu Powder.

J Nanosci Nanotechnol 2021 Sep;21(9):4964-4967

Department of Advanced Materials Science and Engineering, Mokpo National University, Muan 58554, Republic of Korea.

A Cu metal-ceramic filter composite with high thermal conductivity and a suitable thermal expansion coefficient was designed to be applied to high performance heat dissipation materials. The purpose of using the ceramic filler was to decrease the high coefficient of thermal expansion of Cu matrix utilizing the high thermal conductivity of Cu. In this study, a SiC ceramic filler powder was added to the Cu sol including Zn as a liquid phase sintering agent. The final complex was produced by applying a PVB polymer to prepare a homogeneous precursor followed by sintering in a reducing atmosphere. The pressureless sintered composite showed lower thermal conductivity than pure bulk Cu due to the some residual pores. In the case of the Cu-SiC composite in which 10 wt% of SiC filler was added, it showed a thermal conductivity of 100 W/m·°C and a thermal expansion coefficient of 13.3×10/°C. The thermal conductivity showed some difference from the theoretical calculated value due to the pores in the composite, but the thermal expansion coefficient did not show a significant difference.
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http://dx.doi.org/10.1166/jnn.2021.19262DOI Listing
September 2021

Characteristics of Porous YAG:Ce Nano-Powders Phosphor Fabricated by a Solution Combustion Synthesis.

J Nanosci Nanotechnol 2021 Sep;21(9):4886-4890

Department of Advanced Materials Science and Engineering, Mokpo National University, Muan, 58554, Korea.

A cerium-doped YAG (Y₃AlO) phosphor is used as a rare-earth element phosphor for blue light absorption and yellow light emission for a white light source. A solution combustion synthesis, which is a method for producing nano-powder, is a reaction that is spontaneous ignition by reaction heat released through oxidation/reduction reaction between metal nitrate and fuel. Since the reaction speed is fast and it does not go through a separate firing process, it is a method of easily synthesizing nano-powder by simple process. In this study, YAG:Ce nano-powders were prepared by using various fuels in the combustion synthesis method. Depending on the kind of the additive fuel, the reaction of the combustion synthesis process was different, and the shape of the powder particles according to the fuels was also different. The agglomerated particles of nanoparticles were observed and the characteristics of YAG:Ce powders synthesized under various conditions were analyzed.
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http://dx.doi.org/10.1166/jnn.2021.19259DOI Listing
September 2021

Romosozumab in Postmenopausal Korean Women with Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study.

Endocrinol Metab (Seoul) 2021 Feb 24;36(1):60-69. Epub 2021 Feb 24.

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background: This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis.

Methods: Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤-2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months.

Results: At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary efficacy endpoint) between the romosozumab (9.5%) and placebo (-0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P<0.001). The difference in the LS mean percent change from baseline was also significant for total hip and femoral neck BMD (secondary efficacy endpoints). After treatment with romosozumab, the percent change from baseline in procollagen type 1 N-terminal propeptide transiently increased at months 1 and 3, while that in C-terminal telopeptide of type 1 collagen showed a sustained decrease. No events of cancer, hypocalcemia, injection site reaction, positively adjudicated atypical femoral fracture or osteonecrosis of the jaw, or positively adjudicated serious cardiovascular adverse events were observed. At month 9, 17.6% and 2.9% of patients in the romosozumab group developed binding and neutralizing antibodies, respectively.

Conclusion: Treatment with romosozumab for 6 months was well tolerated and significantly increased lumbar spine, total hip, and femoral neck BMD compared with placebo in Korean postmenopausal women with osteoporosis (ClinicalTrials.gov identifier NCT02791516).
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http://dx.doi.org/10.3803/EnM.2020.848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937846PMC
February 2021

Selected nasogastric lavage in patients with nonvariceal upper gastrointestinal bleeding.

BMC Gastroenterol 2021 Mar 6;21(1):113. Epub 2021 Mar 6.

Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, Seoul, Korea.

Background: Risk stratification before endoscopy is crucial for proper management of patients suspected as having upper gastrointestinal bleeding (UGIB). There is no consensus regarding the role of nasogastric lavage for risk stratification. In this study, we investigated the usefulness of nasogastric lavage to identify patients with UGIB requiring endoscopic examination.

Methods: From January 2017 to December 2018, patients who visited the emergency department with a clinical suspicion of UGIB and who underwent nasogastric lavage before endoscopy were eligible. Patients with esophagogastric variceal bleeding were excluded. The added predictive ability of nasogastric lavage to the Glasgow-Blatchford score (GBS) was estimated using category-free net reclassification improvement and integrated discrimination improvement.

Results: Data for 487 patients with nonvariceal UGIB were analyzed. The nasogastric aspirate was bloody in 67 patients (13.8 %), coffee-ground in 227 patients (46.6 %), and clear in 193 patients (39.6 %). The gross appearance of the nasogastric aspirate was associated with the presence of UGIB. Model comparisons showed that addition of nasogastric lavage findings to the GBS improved the performance of the model to predict the presence of UGIB. Subgroup analysis showed that nasogastric lavage improved the performance of the prediction model in patients with the GBS ≤ 11, whereas no additive value was found when the GBS was greater than 11.

Conclusions: Nasogastric lavage is useful for predicting the presence of UGIB in a subgroup of patients, while its clinical utility is limited in high-risk patients with a GBS of 12 or more.
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http://dx.doi.org/10.1186/s12876-021-01690-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937281PMC
March 2021

Transparent, Water-Repellent, Antiviral, Antistatic, and Flexible Cu-Plasma-Polymerized Fluorocarbon Nanocomposite Thin Films.

ACS Appl Mater Interfaces 2021 Mar 16;13(8):10301-10312. Epub 2021 Feb 16.

Chemical Materials Solutions Center, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea.

Polymer thin films containing fluorine are attracting much attention in various high-tech industries owing to their transparency, flexibility, and excellent water repellency. However, the generation of static electricity due to high electrical resistance limits their application. In this study, highly transparent and flexible Cu-plasma-polymerized fluorocarbon (PPFC) nanocomposite thin films that exhibit hydrophobicity and antistatic properties are proposed. These films, obtained using the mid-range frequency sputtering, exhibited a light transmittance of 84.2%, a water contact angle of 94.6°, and a sheet resistance of 1.2 × 10 Ω/□. Transmission electron microscopy and small angle X-ray scattering confirmed that Cu nanoparticles with an average size of 4-5 nm were distributed uniformly in the PPFC matrix. In repeated fatigue bending tests, the Cu-PPFC nanocomposite thin films exhibited excellent mechanical robustness and flexibility. Antiviral properties of the Cu-PPFC nanocomposite thin films were evaluated against influenza A virus, and the number decreased by 96.9% after 30 min. Carbon nanotube-Cu-polytetrafluoroethylene composite targets are advantageous for large-area coating and mass production because they can be applied in large-area sputtering and roll-to-roll processes. The transparency, charging characteristics, and water repellency can be easily controlled in Cu-PPFC nanocomposite thin films by controlling the sputtering power density according to the required product. Therefore, these films can be applied in various industries such as flexible displays, medical, automobiles, functional textiles, and aerospace.
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http://dx.doi.org/10.1021/acsami.0c21247DOI Listing
March 2021

Per- and polyfluoroalkyl substances and their alternatives in black-tailed gull (Larus crassirostris) eggs from South Korea islands during 2012-2018.

J Hazard Mater 2021 06 6;411:125036. Epub 2021 Jan 6.

Department of Civil and Environmental Engineering, Pusan National University, Busan 46241, Republic of Korea. Electronic address:

The temporal and spatial trends of sixteen per- and polyfluoroalkyl substances (PFAS) and their three alternatives, chlorinated polyfluoroalkyl ether sulfonic acid (F-53B), hexafluoropropylene oxide dimer acid (GenX), and dodecafluoro-3H-4,8-dioxanonanoate (ADONA) in whole eggs of black-tailed gulls from two South Korean islands, Baengnyeongdo (BLD) and Hongdo (HD), were investigated during 2012-2018. A total of 16 analyzed compounds were detected at concentrations of 21.3-47.8 ng/g ww in BLD and 11.2-40.0 ng/g ww in HD. Meanwhile, the mean levels of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) were detected at 6.92 ± 4.72 ng/g ww and 0.674 ± 0.993 ng/g ww, respectively. In particular, F-53B, a major alternative to PFOS was detected in each year of the study period with a level of up to 6.66 ng/g ww in all egg samples. Significant increasing temporal trends were observed for PFOS, perfluorononanoic acid (PFNA) and one alternative (F-53B) during the investigated period suggesting continuous use or accumulation of these in the Korean environment. Moreover, distinctive spatial distribution patterns such as a significantly higher F-53B level in HD and an increased PFAS (< C11) in BLD were also observed.
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http://dx.doi.org/10.1016/j.jhazmat.2020.125036DOI Listing
June 2021

Novel Medicine for Endometriosis and Its Therapeutic Effect in a Mouse Model.

Biomedicines 2020 Dec 16;8(12). Epub 2020 Dec 16.

CHA Fertility Center Seoul Station, Seoul 04637, Korea.

Current therapeutic medicines for endometriosis cannot be administered during assisted reproductive technology (ART) because they have bad effects during pregnancy. In this study, we created an animal model of endometriosis and evaluated the therapeutic effect of progestin (Dienogest), dopamine agonist (Cabergoline), and their combination (Dienogest + Cabergoline). We established a mouse model mimicking human endometriosis. The mice with endometriosis were then treated with a single drug (Dienogest or Cabergoline) or both drugs (Dienogest + Cabergoline) for 14 days. An immunohistological study was then performed to analyze inflammatory lesions in the recipient mice. Real-time polymerase chain reaction (RT-PCR) and Western blotting were also performed to determine the levels of genes and proteins in inflammatory lesions to assess the recovery of endometriosis. Histologic staining showed that all medication groups showed a clear decrease in the inflammatory phenotype in the uterus, peritoneum, and intestine. Gene and protein expression analysis showed a therapeutic effect in all medication groups. In conclusion, Cabergoline had a therapeutic effect similar to that of Dienogest and could be used as an alternative to Dienogest during ART for patients with infertility; compared to the individual drugs, the combination treatment has a synergistic effect on endometriosis.
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http://dx.doi.org/10.3390/biomedicines8120619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766695PMC
December 2020

A photo-crosslinkable cartilage-derived extracellular matrix bioink for auricular cartilage tissue engineering.

Acta Biomater 2021 02 21;121:193-203. Epub 2020 Nov 21.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Electronic address:

Three-dimensional (3D) bioprinting of patient-specific auricular cartilage constructs could aid in the reconstruction process of traumatically injured or congenitally deformed ear cartilage. To achieve this, a hydrogel-based bioink is required that recapitulates the complex cartilage microenvironment. Tissue-derived decellularized extracellular matrix (dECM)-based hydrogels have been used as bioinks for cell-based 3D bioprinting because they contain tissue-specific ECM components that play a vital role in cell adhesion, growth, and differentiation. In this study, porcine auricular cartilage tissues were isolated and decellularized, and the decellularized cartilage tissues were characterized by histology, biochemical assay, and proteomics. This cartilage-derived dECM (cdECM) was subsequently processed into a photo-crosslinkable hydrogel using methacrylation (cdECMMA) and mixed with chondrocytes to create a printable bioink. The rheological properties, printability, and in vitro biological properties of the cdECMMA bioink were examined. The results showed cdECM was obtained with complete removal of cellular components while preserving major ECM proteins. After methacrylation, the cdECMMA bioinks were printed in anatomical ear shape and exhibited adequate mechanical properties and structural integrity. Specifically, auricular chondrocytes in the printed cdECMMA hydrogel constructs maintained their viability and proliferation capacity and eventually produced cartilage ECM components, including collagen and glycosaminoglycans (GAGs). The potential of cell-based bioprinting using this cartilage-specific dECMMA bioink is demonstrated as an alternative option for auricular cartilage reconstruction.
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http://dx.doi.org/10.1016/j.actbio.2020.11.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855948PMC
February 2021

Prognostic Implication of SOX2 Expression Associated with p16 in Oropharyngeal Cancer: A Study of Consecutive Tissue Microarrays and TCGA.

Biology (Basel) 2020 Nov 9;9(11). Epub 2020 Nov 9.

Department of Otorhinolaryngology-Head and Neck Surgery, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, Gyeonggi-do, Korea.

For oropharyngeal squamous cell carcinoma (OPSCC), there are not enough additional robust biomarkers for subgrouping after the distinct classification using p16. As SOX2 is an emerging biomarker for cancer treatment, its clinical implication in OPSCC was evaluated using a consecutive tissue microarray (TMA) cohort consisting of 111 patients who underwent surgery as an initial treatment from May 2002 to December 2016 and 79 patients in The Cancer Genome Atlas (TCGA) dataset. In both datasets, p16+ (HPV+/ in TCGA) showed the best prognosis among the four groups classified by SOX2 and p16 for 5-year overall survival (OS) and recurrence (all < 0.05), but SOX2 did not make a significant difference in the prognosis of the p16- group. In the TMA cohort, SOX2 was significantly correlated with response to radiotherapy and lower pathologic T classification in the p16+ group ( = 0.001). In TCGA, correlations between and tumor stage classification or radiotherapy were not observed; however, HPV+/ had a significantly low tumor mutation burden among the four groups (all < 0.05). In summary, SOX2 was proven to be a potential marker to predict overall survival and recurrence in p16+ OPSCC. However, the role of SOX2 has not yet been confirmed in p16- OPSCC patients.
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http://dx.doi.org/10.3390/biology9110387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695281PMC
November 2020

3D Printing and NIR Fluorescence Imaging Techniques for the Fabrication of Implants.

Materials (Basel) 2020 Oct 28;13(21). Epub 2020 Oct 28.

Nano-Bio Regenerative Medical Institute, College of Medicine, Hallym University, Chuncheon 24252, Korea.

Three-dimensional (3D) printing technology holds great potential to fabricate complex constructs in the field of regenerative medicine. Researchers in the surgical fields have used 3D printing techniques and their associated biomaterials for education, training, consultation, organ transplantation, plastic surgery, surgical planning, dentures, and more. In addition, the universal utilization of 3D printing techniques enables researchers to exploit different types of hardware and software in, for example, the surgical fields. To realize the 3D-printed structures to implant them in the body and tissue regeneration, it is important to understand 3D printing technology and its enabling technologies. This paper concisely reviews 3D printing techniques in terms of hardware, software, and materials with a focus on surgery. In addition, it reviews bioprinting technology and a non-invasive monitoring method using near-infrared (NIR) fluorescence, with special attention to the 3D-bioprinted tissue constructs. NIR fluorescence imaging applied to 3D printing technology can play a significant role in monitoring the therapeutic efficacy of 3D structures for clinical implants. Consequently, these techniques can provide individually customized products and improve the treatment outcome of surgeries.
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http://dx.doi.org/10.3390/ma13214819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662749PMC
October 2020

Comparison Study of Stem Cell-Derived Extracellular Vesicles for Enhanced Osteogenic Differentiation.

Tissue Eng Part A 2020 Nov 19. Epub 2020 Nov 19.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Stem cell-derived extracellular vesicles (EVs) have shown great promise in the field of regenerative medicine and tissue engineering. Recently, human bone marrow-derived mesenchymal stem cell (BMSC)-derived EVs have been considered for bone tissue engineering applications. In this study, we evaluated the osteogenic capability of placental stem cell (PSC)-derived EVs and compared them to the well-characterized BMSC-derived EVs. EVs were extracted from three designated time points (0, 7, and 21 days) after osteogenic differentiation. The results showed that the PSC-derived EVs had much higher protein and lipid concentrations than EVs derived from BMSCs. The extracted EVs were characterized by observing their morphology and size distribution before utilizing next-generation sequencing to determine their microRNA (miRNA) profiles. A total of 306 miRNAs within the EVs were identified, of which 64 were significantly expressed in PSC-derived EVs that related to osteogenic differentiation. osteogenic differentiation study indicated the late-stage (21-day extracted)-derived EVs higher osteogenic enhancing capability when compared with the early stage-derived EVs. We demonstrated that EVs derived from PSCs could be a new source of EVs for bone tissue engineering applications.
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http://dx.doi.org/10.1089/ten.TEA.2020.0194DOI Listing
November 2020

The Influence of Printing Parameters and Cell Density on Bioink Printing Outcomes.

Tissue Eng Part A 2020 Dec 14;26(23-24):1349-1358. Epub 2020 Oct 14.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Bioink printability persists as a limiting factor toward many bioprinting applications. Printing parameter selection is largely user-dependent, and the effect of cell density on printability has not been thoroughly investigated. Recently, methods have been developed to give greater insight into printing outcomes. This study aims to further advance those methods and apply them to study the effect of printing parameters (feedrate and flowrate) and cell density on printability. Two printed structures, a crosshatch and five-layer tube, were established as printing standards and utilized to determine the printing outcomes. Acellular bioinks were printed using a testing matrix of feedrates of 37.5, 75, 150, 300, and 600 mm/min and flowrates of 21, 42, 84, 168, and 336 mm/min. Structures were also printed with cell densities of 5, 10, 20, and 40 × 10 cell/mL at 150 mm/min and 84 mm/min. Only speed ratios (defined as flowrate divided by feedrate) from 0.07 to 2.24 mm were suitable for analysis. Increasing speed ratio dramatically increased the height, width, and wall thickness of tubular structures, but did not influence radial accuracy. For crosshatch structures, the area of pores and the frequency of broken filaments were decreased without impacting pore shape (). Within speed ratios, feedrate and flowrate had negligible, inconsistent effects. Cell density did not affect any printing outcomes despite slight rheological changes. Printing outcomes were dominated by the speed ratio, with feedrate, flowrate, and cell density having little impact on printing outcomes when controlling for speed ratio within the ranges tested. The relevance of these results to other bioinks and printing conditions requires continued investigation by the bioprinting community, as well as highlight speed ratio as a key variable to report and suggest that rheology is a more sensitive measure than printing outcomes.
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http://dx.doi.org/10.1089/ten.TEA.2020.0210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780841PMC
December 2020

CMOS Depth Image Sensor with Offset Pixel Aperture Using a Back-Side Illumination Structure for Improving Disparity.

Sensors (Basel) 2020 Sep 9;20(18). Epub 2020 Sep 9.

School of Electronics Engineering, Kyungpook National University, 80 Deahak-ro, Buk-gu, Daegu 41566, Korea.

This paper presents a CMOS depth image sensor with offset pixel aperture (OPA) using a back-side illumination structure to improve disparity. The OPA method is an efficient way to obtain depth information with a single image sensor without additional external factors. Two types of apertures (i.e., left-OPA (LOPA) and right-OPA (ROPA)) are applied to pixels. The depth information is obtained from the disparity caused by the phase difference between the LOPA and ROPA images. In a CMOS depth image sensor with OPA, disparity is important information. Improving disparity is an easy way of improving the performance of the CMOS depth image sensor with OPA. Disparity is affected by pixel height. Therefore, this paper compared two CMOS depth image sensors with OPA using front-side illumination (FSI) and back-side illumination (BSI) structures. As FSI and BSI chips are fabricated via different processes, two similar chips were used for measurement by calculating the ratio of the OPA offset to pixel size. Both chips were evaluated for chief ray angle (CRA) and disparity in the same measurement environment. Experimental results were then compared and analyzed for the two CMOS depth image sensors with OPA.
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http://dx.doi.org/10.3390/s20185138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570693PMC
September 2020

Physical and Chemical Factors Influencing the Printability of Hydrogel-based Extrusion Bioinks.

Chem Rev 2020 10 20;120(19):10834-10886. Epub 2020 Aug 20.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, United States.

Bioprinting researchers agree that "printability" is a key characteristic for bioink development, but neither the meaning of the term nor the best way to experimentally measure it has been established. Furthermore, little is known with respect to the underlying mechanisms which determine a bioink's printability. A thorough understanding of these mechanisms is key to the intentional design of new bioinks. For the purposes of this review, the domain of printability is defined as the bioink requirements which are unique to bioprinting and occur during the printing process. Within this domain, the different aspects of printability and the factors which influence them are reviewed. The extrudability, filament classification, shape fidelity, and printing accuracy of bioinks are examined in detail with respect to their rheological properties, chemical structure, and printing parameters. These relationships are discussed and areas where further research is needed, are identified. This review serves to aid the bioink development process, which will continue to play a major role in the successes and failures of bioprinting, tissue engineering, and regenerative medicine going forward.
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http://dx.doi.org/10.1021/acs.chemrev.0c00015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673205PMC
October 2020

Inhaled underground subway dusts may stimulate multiple pathways of cell death signals and disrupt immune balance.

Environ Res 2020 12 15;191:109839. Epub 2020 Aug 15.

Jeonbuk Branch Institute, Korea Institute of Toxicology, Jeongeup, South Korea. Electronic address:

In this study, we aimed to identify a toxic mechanism and the potential health effects of ambient dusts in an underground subway station. At 24 h exposure to human bronchial epithelial (BEAS-2B) cells (0, 2.5, 10, and 40 μg/mL), dusts located within autophagosome-like vacuoles, whereas a series of autophagic processes appeared to be blocked. The volume, potential and activity of mitochondria decreased in consistent with a condensed configuration, and the percentage of late apoptotic cells increased accompanying S phase arrest. While production of reactive oxygen species, expression of ferritin (heavy chain) protein, secretion of IL-6, IL-8 and matrix metalloproteinases, and the released LDH level notably increased in dust-treated cells (40 μg/mL), intracellular calcium level decreased. At day 14 after a single instillation to mice (0, 12.5, 50, and 200 μg/head), the total number of cells increased in the lungs of dust-treated mice with no significant change in cell composition. The pulmonary levels of TGF-β, GM-CSF, IL-12 and IL-13 clearly increased following exposure to dusts, whereas that of CXCL-1 was dose-dependently inhibited. Additionally, the population of cytotoxic T cells in T lymphocytes in the spleen increased relative to that of helper T cells, and the levels of IgA and IgM in the bloodstream were significantly reduced in the dust-treated mice. Subsequently, to improve the possibility of extrapolating our findings to humans, we repeatedly instilled dusts (1 time/week, 4 weeks, 0.25 and 1.0 mg/head) to monkeys. The total number of cells, the relative portion of neutrophils, the level of TNF-α significantly increased in the lungs of dust-treated monkeys, and the expression of cytochrome C was enhanced in the lung tissues. Meanwhile, the pulmonary level of MIP-α was clearly reduced, and the expression of caveolin-1 was inhibited in the lung tissues. More importantly, inflammatory lesions, such as granuloma, were seen in both mice and monkeys instilled with dusts. Taken together, we conclude that dusts may impair the host's immune function against foreign bodies by inhibiting the capacity for production of antibodies. In addition, iron metabolism may be closely associated with dust-induced cell death and inflammatory response.
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http://dx.doi.org/10.1016/j.envres.2020.109839DOI Listing
December 2020

NIR fluorescence for monitoring in vivo scaffold degradation along with stem cell tracking in bone tissue engineering.

Biomaterials 2020 11 6;258:120267. Epub 2020 Aug 6.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA. Electronic address:

Stem cell-based tissue engineering has the potential to use as an alternative for autologous tissue grafts; however, the contribution of the scaffold degradation along with the transplanted stem cells to in vivo tissue regeneration remains poorly understood. Near-infrared (NIR) fluorescence imaging has great potential to monitor implants while avoiding autofluorescence from the adjacent host tissue. To utilize NIR imaging for in vivo monitoring of scaffold degradation and cell tracking, we synthesized 800-nm emitting NIR-conjugated PCL-ran-PLLA-ran-PGA (ZW-PCLG) copolymers with three different degradation rates and labeled 700-nm emitting lipophilic pentamethine (CTNF127) on the human placental stem cells (CT-PSCs). The 3D bioprinted hybrid constructs containing the CT-PSC-laden hydrogel together with the ZW-PCLG scaffolds demonstrate that NIR fluorescent imaging enables tracking of in vivo scaffold degradation and stem cell fate for bone regeneration in a rat calvarial bone defect model. This NIR-based monitoring system can be effectively utilized to study cell-based tissue engineering applications.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484145PMC
November 2020