Objective
Rebamipide, a gastroprotective agent, has the ability to scavenge reactive oxygen radicals. Increased oxidative stress is implicated in the pathogenesis of rheumatoid arthritis (RA). We ...undertook this study to investigate the impact of rebamipide on the development of arthritis and the pathophysiologic mechanisms by which rebamipide attenuates arthritis severity in a murine model of RA.
Methods
Collagen‐induced arthritis (CIA) was induced in DBA/1J mice. Anti–type II collagen antibody titers and interleukin‐17 (IL‐17) levels were determined using enzyme‐linked immunosorbent assay. The expression of transcription factors was analyzed by immunostaining and Western blotting. Frequencies of IL‐17–producing CD4+ T cells (Th17 cells) and CD4+CD25+FoxP3+ Treg cells were analyzed by flow cytometry.
Results
Rebamipide reduced the clinical arthritis score and severity of histologic inflammation and cartilage destruction in a dose‐dependent manner. The joints isolated from rebamipide‐treated mice with CIA showed decreased expression of nitrotyrosine, an oxidative stress marker. Rebamipide‐treated mice showed lower circulating levels of type II collagen–specific IgG, IgG1, and IgG2a. Whereas the number of Th17 cells in spleens was decreased in rebamipide‐treated mice with CIA, a significant increase in the number of Treg cells in spleens was observed. In vitro, rebamipide inhibited Th17 cell differentiation through STAT‐3/retinoic acid receptor–related orphan nuclear receptor γt and reciprocally induced Treg cell differentiation through FoxP3. Rebamipide increased Nrf2 nuclear activities in murine CD4+ T cells and LBRM‐33 murine T lymphoma cells. Heme oxygenase 1 (HO‐1) expression in the spleens was markedly increased in rebamipide‐treated mice.
Conclusion
The inhibitory effects of rebamipide on joint inflammation are associated with recovery from an imbalance between Th17 cells and Treg cells and with activation of an Nrf2/HO‐1 antioxidant pathway.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Solute carrier family 26 member 4 (SLC26A4) is a member of the SLC26A transporter family and is expressed in various tissues, including the airway epithelium, kidney, thyroid, and tumors. It ...transports various ions, including bicarbonate, chloride, iodine, and oxalate. As a multiple-ion transporter, SLC26A4 is involved in the maintenance of hearing function, renal function, blood pressure, and hormone and pH regulation. In this review, we have summarized the various functions of SLC26A4 in multiple tissues and organs. Moreover, the relationships between SLC26A4 and other channels, such as cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and sodium chloride cotransporter, are highlighted. Although the modulation of SLC26A4 is critical for recovery from malfunctions of various organs, development of specific inducers or agonists of SLC26A4 remains challenging. This review contributes to providing a better understanding of the role of SLC26A4 and development of therapeutic approaches for the SLC26A4-associated hearing loss and SLC26A4-related dysfunction of various organs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In the quest for renewable and highly efficient energy storage devices, all-lignin-based flexible supercapacitors are fabricated by integrating chemically cross-linked lignin hydrogel electrolytes ...with electrospun lignin/polyacrylonitrile nanofiber electrodes. The cross-linked networks of lignin-based hydrogel electrolytes show high ionic conductivity and mechanical integrity, whereas the free-standing flexible composite electrode achieves outstanding charge storage capability and kinetics arising from interconnected porous channels. The resulting devices demonstrate a high capacitance of 129.23 F g
−1
and capacitance retention of 95% over 10 000 cycles as well as flexibility and durability under diverse bending angles. Moreover, these renewable flexible supercapacitors deliver a maximum energy and power density of 4.49 W h kg
−1
and 2.63 kW kg
−1
, respectively.
In the quest for renewable and highly efficient energy storage devices, all-lignin-based flexible supercapacitors are fabricated by integrating cross-linked lignin hydrogel electrolytes with electrospun lignin/polyacrylonitrile nanofiber electrodes.
Planetary boundary layer (PBL) flow over complex terrain during a cold surge event was investigated using 3-hourly radiosonde measurements in upwind, near ridge, and downwind locations of mountains ...in the northeastern part of Republic of Korea and using a high-resolution (333-m) numerical simulation. A cold surge occurred on 23 January 2018 and lasted for 4 days. We analyzed onset day of the cold surge when air temperature dropped rapidly. Analysis of the radiosonde data shows that the PBL was characterized by an adiabatic layer with strong capping inversion in early morning and evening as well as during daytime in the upwind and near-ridge sites. The PBL flow at the near-ridge site was strongest among three sites except at 0600 local standard time (LST) when the PBL flow in the lee was strongest. We performed high-resolution (333-m) numerical simulations using the Weather Research and Forecasting (WRF) model. The adiabatic PBL in the upwind site at 0600 LST was simulated, although its depth was underestimated. The model reproduced the strong low-level wind at 0600 LST and large wind shear during the daytime in the lee, but it did not capture the exact timing of the large wind shear. The model showed overall good performance in simulating the vertical profile of the virtual potential temperature and wind below 2 km above ground level at the three sites, with a high index of agreement (IOA) except for the wind at 1200 and 1500 LST in the lee. To examine the cause for the different behavior of PBL flow in the lee of mountains between 0600 LST and the daytime, we calculated the Froude number for PBL flow using radiosonde measurements based on reduced gravity shallow water (RGSW) theory. At 0600 LST, the upwind Froude number F0 was close to 1, while during the daytime, it was much lower than 1. The observed lee flow behavior was consistent with the flow regime change of a single layer over an obstacle with changing F0; the flow with a propagating lee jump changes into that with a stationary lee jump with decreasing F0. Numerical simulation shows that the steepening of streamlines of lee-wave field leads to a jump-like structure in the lee of mountains during the daytime.
Breast cancer is the most commonly diagnosed cancer worldwide and ranks first in terms of both prevalence and cancer-related mortality in women. In this study, we aimed to evaluate the anticancer ...effect of mebendazole (MBZ) and radiotherapy (RT) concomitant use in triple-negative breast cancer (TNBC) cells and elucidate the underlying mechanisms of action. Breast cancer mouse models and several types of breast cancer cells, including TNBC-derived RT-resistant (RT-R) MDA-MB-231 cells, were treated with MBZ and/or RT. In mice, changes in body weight, renal and liver toxicity, tumor volume, and number of lung metastases were determined. In cells, cell viability, colony formation, scratch wound healing, Matrigel invasion, and protein expression using western blotting were determined. Our findings showed that MBZ and RT combined treatment increased the anticancer effect of RT without additional toxicity. In addition, we noted that cyclin B1, PH2AX, and natural killer (NK) cell-mediated cytotoxicity increased following MBZ + RT treatment compared to unaided RT. Our results suggest that MBZ + RT have an enhanced anticancer effect in TNBC which acquires radiation resistance through blocking cell cycle progression, initiating DNA double-strand breaks, and promoting NK cell-mediated cytotoxicity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Sugammadex is known to reverse neuromuscular blockade induced by non-depolarizing agents. In children, the recommended dose for reversal of moderate neuromuscular blockade is 2 mg/kg. We investigated ...the pharmacokinetics and pharmacodynamics of sugammadex in Korean children.
Children (2-17 years of age) undergoing brain or spine surgery were enrolled and randomly assigned to control (neostigmine) and 2, 4, or 8 mg/kg sugammadex groups. Following induction of anesthesia and monitoring of the response to train-of-four stimulation, 1 mg/kg rocuronium was intravenously administered. Upon reappearance of the second twitch to train-of-four stimulation, the study drug was administered according to group allocation. The plasma concentrations of rocuronium and sugammadex were serially measured at nine predefined time points following study drug administration. To determine efficacy, we measured the time elapsed from drug administration to recovery of T
/T
≥ 0.9. For pharmacokinetics, non-compartmental analysis was performed and we monitored adverse event occurrence from the time of study drug administration until 24 h post-surgery.
Among the 29 enrolled participants, the sugammadex (2 mg/kg) and control groups showed recovery times median (interquartile range) of 1.3 (1.0-1.9) and 7.7 (5.3-21.0) min, respectively (
= 0.002). There were no significant differences in recovery time among the participants in sugammadex groups. The pharmacokinetics of sugammadex were comparable to those of literature findings. Although two hypotensive events related to sugammadex were observed, no intervention was necessary.
The findings of this pharmacokinetic analysis and efficacy study of sugammadex in Korean children indicated that sugammadex (2 mg/kg) may be safely administered for reversing moderate neuromuscular blockade. Some differences in pharmacokinetics of sugammadex were observed according to age.
http://clinicaltrials.gov (NCT04347486).
Crude polysaccharides, extracted from two seaweed species (
and
) and
(abalone) viscera, were evaluated for their inhibitory effect against SARS-CoV-2 propagation. Plaque titration revealed that ...these crude polysaccharides efficiently inhibited SARS-CoV-2 propagation with IC
values ranging from 0.35 to 4.37 μg/mL. The crude polysaccharide of
showed the strongest antiviral effect, with IC
of 0.35 μg/mL, followed by
and abalone viscera with IC
of 0.56 and 4.37 μg/mL, respectively. In addition, immunofluorescence assay, western blot, and quantitative RT-PCR analysis verified that these polysaccharides could inhibit SARS-CoV-2 replication. In Vero E6 cells, treatment with these crude polysaccharides before or after viral infection strongly inhibited the expression level of SARS-CoV-2 spikes, nucleocapsid proteins, and RNA copies of RNA-dependent RNA-polymerase and nucleocapsid. These results show that these crude marine polysaccharides effectively inhibit SARS-CoV-2 propagation by interference with viral entry.
A wavelength-selective tunable plasmonic absorber is required for various applications, such as thermal imaging sensors, active biosensors, and switching devices in integrated optics. Using Ge 2 Sb 2 ...Te 5 (GST), which is a representative phase change material showing a large change in optical characteristics, we propose a tunable plasmonic absorber that consists of a metal nanoslit array patterned on a GST-inserted dielectric layer. Based on systematic optimization, the proposed structure achieved a nearly zero reflectance for both states of the inserted GST film with a very large resonance shift after the phase transition. Moreover, the resonance wavelength of the proposed absorber could be flexibly tuned within a broad near-infrared range by tuning the geometric conditions of the nanoslit array and the thicknesses of the dielectric-GST-dielectric multilayer.
Dexmedetomidine (Dex) has analgesic and sedative properties and anti-inflammatory functions. Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the ...interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been fully studied. Inflamed and migrated fibroblast-like synoviocytes (FLSs) are involved in RA severity. Thus, we aimed to determine the effects of Dex on RA-FLSs treated with inflammatory cytokines and a growth factor as multiple stimulating inputs. TNF-α, IL-6, and EGF as multiple stimulating inputs increased the cAMP concentration of RA-FLSs, while Dex treatment reduced cAMP concentration. Dex reduced electroneutral sodium-bicarbonate cotransporter 1 (NBCn1) expression, NBC activity, and subsequent RA-FLS migration. The mRNA expression levels of RA-related factors, such as inflammatory cytokines and osteoclastogenesis factors, were enhanced by multiple-input treatment. Notably, Dex effectively reduced these expression levels in RA-FLSs. These results indicate that multiple inflammatory or stimulating inputs enhance RA-FLS migration, and treatment with Dex relieves activated RA-FLSs, suggesting that Dex is a potential therapeutic drug for RA.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To design an easily manufactured, large energy density, highly reversible, and fast rate-capable Li-ion battery (LIB) anode, Co–Sn intermetallics (CoSn2, CoSn, and Co3Sn2) were synthesized, and their ...potential as anode materials for LIBs was investigated. Based on their electrochemical performances, CoSn2 was selected, and its C-modified nanocomposite (CoSn2/C) as well as Ti- and C-modified nanocomposite (CoSn2/a-TiC/C) was straightforwardly prepared. Interestingly, the CoSn2, CoSn2/C, and CoSn2/a-TiC/C showed conversion/nonrecombination, conversion/partial recombination, and conversion/full recombination during Li insertion/extraction, respectively, which were thoroughly investigated using ex situ X-ray diffraction and extended X-ray absorption fine structure analyses. As a result of the interesting conversion/full recombination mechanism, the easily manufactured CoSn2/a-TiC/C nanocomposite for the Sn-based Li-ion battery anode showed large energy density (first reversible capacity of 1399 mAh cm–3), high reversibility (first Coulombic efficiency of 83.2%), long cycling behavior (100% capacity retention after 180 cycles), and fast rate capability (appoximately 1110 mAh cm–3 at 3C rate). In addition, degradation/enhancement mechanisms for high-capacity and high-performance Li-alloy-based anode materials for next-generation LIBs were also suggested.
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IJS, KILJ, NUK, PNG, UL, UM
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